Coronaviruses are positive-stranded RNA viruses that may exert severely negative effects on the mortality and morbidity of a broad range of birds and mammals including humans and domestic animals. The strain called SARS-CoV-2 host-switched from bats to humans in Wuhan, China in November 2019 and subsequently gave rise to a devastating global pandemic called CoVID-191,2,3. Susceptibility of human societies appear to be markedly heterogeneous ranging from modest to very high morbidity. Contrary to general expectations, more developed, wealthier communities living under better hygienic conditions appear to be more threatened than others. Thus, Austria is seemingly more severely hit than Hungary, the Czech Republic than Slovakia, and Israel than Palestine or Jordan.
Evidently, the first step to search for factors influencing this pandemic is to identify environmental correlates of different populations’ susceptibility. Sala and Miyakawa4 suggested that the different BCG vaccination policies across countries may partly explain differences in susceptibility to CoVID-19. Indeed, higher morbidity and mortality is observed in societies with no obligatory BCG vaccination. However, vaccination schemes tend to be uniform within countries, thus this hypothesis cannot explain the huge within-country differences that are often observed, such as those between Northern vs. Southern Italy. Zhu et al.5 described a covariation between exposure to air pollution and CoVID-19 infection.
We hypothesize that certain common infections coming together with a less hygienic lifestyle may trigger the human immune system and thus facilitate some protection against CoVID-19, an argument similar to the so-called ‘hygiene hypothesis’6. Toxoplasmosis is a candidate infection for this purpose because of two reasons. First, it is one of the most widespread latent infections of humanity7,8. As it does not transmit from human to human, its prevalence can be interpreted as a generalized index of group hygiene. Second, its causative agent, the eukaryotic protozoan Toxoplasma gondii, is known to exhibit at least some antiviral effects9.
Toxoplasma gondii is an intracellular parasite that infects birds and mammals as intermediate hosts, while the sexual phase of its life cycle can only be completed in feline definitive hosts, most often in domestic cats. It is distributed in human societies mostly by semi-domestic, partly-feral cats that depredate on infected rodents and birds and then eat their prey. Subsequently, the infective spores are released through their faeces and may get into direct contact with humans to cause infections. Alternatively, domestic animals may be infected by these spores and the consumption of their infected meat transmits T. gondii to humans. Thus, humans act like intermediate hosts, although they are not depredated by cats, and thus this is a dead-end for the parasites. ‘Luxury cats’ living on canned pet-food throughout their life may not transmit this infection. Asymptomatic infections are common in humans, especially among those living in the proximity of semi-feral domestic cats10.
Toxoplasma gondii excretes Dense Granule Protein-7 (GRA-7) into the host cell that inhibits viral replication. Its effect has been proven both in vitro and in vivo against indiana vesiculovirus, influenza A virus, Coxsackie virus, and herpes simplex virus. Overall, GRA-7 exhibits immune-stimulatory and a broad spectrum of antiviral activities via type I interferons signaling9. Moreover, in response to T. gondii infection, laboratory mice highly upregulate Immune Responsive Gene 1 in their lungs11. This is an interferon-stimulated gene that mediates antiviral effects against RNA viruses like the West Nile and Zika viruses through its product named itaconate12. It has been established that GRA-7 could be serve as alternative to treat tuberculosis13.
We need to emphasize, however, that the antiviral activities of Toxoplasma gondii are limited to the first, short and virulent phase of the infection, and not known to operate through the subsequent latent period that may last through the whole life of the host. Therefore, even in societies where a large proportion of the population carries latent toxoplasmosis, the proportion of infections actually expressing antiviral activities is very low. Thus we only claim that Toxoplasma gondii expresses at least some antiviral adaptations. Moreover, the apicoplast proteins of Toxoplasma are known to have immunogenic potential14.
Finally, we chose toxoplasmosis out of the candidate human infections partly because the availability of prevalence data from as many countries as possible. Unfortunately, as in the case of all other human infections, the methodologies of gathering and evaluating epidemiological data can be quite heterogeneous across countries. Below we set out to test whether there is a negative co-variation between levels of toxoplasmosis and CoVID-19 pandemic at a global scale.
Source: Ecology - nature.com
