Rhinolophus affinis (photo: Sanjeev Baniya)

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Bats and Covid-19

April 2020, by Sanjeev Baniya.

Bats do not spread and have very wrongly been blamed for COVID-19 pandemic. There aren’t any conclusive evidence to verify the origination of SARS-CoV-2. Although the virus SARS-CoV-2 resembles the virus RatG13 virus in Intermediate Horseshoe bat (Rhinolophus affinis), there are major differences in the spike protein and polybasic cleavage sites. For human transmission through Ace2 receptors, the spike proteins play a significant role. It is true that bats are carrier of diseases but they have evolved to suppress them through metabolism and heat produced during flights and a super-immune system.  When any wildlife experiences stress as a result of habitat loss, fragmentation, hunting and culling; the diseases contained in them can emerge. Humans are the major drivers of stress in wildlife. We should therefore learn from it, study species such as bats, ensure effective conservation of species and habitat, abandon wet markets and appreciate the ecological services and balance provided by all the species to ensure that these kind of viral outbreaks don’t happen in the future.

Introduction– In this current pandemic of COVID-19, there’s not a thing more insanely maligned than bats. The second most diverse group of mammals with more than 1400 species (Burgin et al., 2018) and cosmopolitan except for Antarctica means the people blaming them as a culprit are everywhere. One common thing that we always seem to forget is how we have been living together with these mammals for ages. We can ponder on what’s changed. Well, I’ve never heard of a bat cutting down trees and modifying forests to agricultural lands nor have seen them hunting humans and eating them.

Bats and Flight– Bats are the only mammals with sustained true flight. Their flight mechanism not only helps them forage but also fight diseases and viruses (O’Shea et al., 2014). The production of reactive oxygen molecules after the mitochondria goes into overdrive in flight helps the immune system to rouse immune cells and kill invaders. This high magnitude of reactive oxygen molecules (oxidative stress), however, can weaken cell membranes, proteins and even break DNA. But bats have evolved accordingly. Genetic studies have confirmed that genetic mutation (concentration of positively selected genes in the DNA) in bats helps boost their ability to detect, repair and prevent replication of damaged DNA (Zhang et al., 2013). This, however, cannot repair the entirety of damaged DNA and thus could trigger an inflammation immune response as seen in most mammals. Acute inflammatory response helps get rid of invaders and helps in healing. Bats, however, are exposed to this for a prolonged period while on flight and could well have been subjected to organ failures and death. So how could they still be alive? In order to tackle this acute inflammation, bats have evolved in such a way that they lack genes for Pyhin protein, a protein responsible for inflammation triggering sensors (Zhang et al., 2013). Similarly, the huge amount of heat produced while on a flight also helps them fight against viral diseases forestalling any viral replication and increasing immune efficiency (Canale and Henry, 2011). Some viruses which develop resistance against rapid metabolisms and increased heat become deadly when they spillover to other animals.

Bats- carriers of diseases– Their very low inflammatory response means that bats are open to all types of pathogens and are known to be reservoirs. They may have a viral infection but won’t show any symptoms like in humans mainly because these viruses are short lived in bats. The cellular defense genes, interferon alpha genes, always remain activated in bats which could potentially kill the viruses in their early phase (Baker et al., 2013). An enzyme Ribonuclease L when activated chops up viral RNA to stop a pathogen from multiplication and spreading. Bats are very quick to activate this enzyme. Although, the virus is short lived, it could linger in a population through actions of grooming and congregations. The low inflammatory response could also be the reason that a plethora of bats are killed by fungus Pseudogymnoascus destructans, which causes the white nose syndrome disease. Unfortunately, nobody talks about how this fungus came to North America from caves of Europe and Asia and killed millions of bats. Bats could never migrate such long distances. Who could? Humans.

Don’t blame bats for COVID-19 pandemic– After all this background, now let’s get to the actual topic of discussion. The spillover of zoonotic diseases from bats to the human population doesn’t just occur without any stress component. When bats get stressed through different mechanisms such as habitat loss, arousals from hibernation, hunting etc., this stress temporarily dampens its antiviral systems, allowing any hidden viruses to emerge. And when these viruses get an intermediate host (camels in MERS, pigs in Nipah, civets in SARS, horse in Hendra virus), they can potentially transmit to human populations. In the case of the current virus SARS-COV-2 causing COVID-19, it is BELIEVED that the natural host of the virus are bats and that they were first transmitted to Pangolins in a wet market in Wuhan thus gaining a spike protein for human transmission. As of today, nothing can be said for certain about its origination and it is also unlikely that humans got this virus from bats. SARS-CoV-2 differs from related viruses in: 1) mutations in the receptor binding domain (six RBD amino acids present in the binding region of SARS-CoV2 helps them bind with ACE2 receptors) and 2) polybasic furin cleavage site and O-linked glycans which together play a role in determining viral infectivity and host range (Andersen et al., 2020). Although the virus is ~96% similar to the RatG13 virus in intermediate horseshoe bat (Rhinolophus affinis), the major difference lie in their spike protein in the Receptor Binding Domain (RBD) suggesting that RatG13 may not bind efficiently with human ACE2 receptors. This RBD region happens to show strong similarity with the Pangolin corona viruses. However, known bat corona viruses and pangolin corona viruses have, both, lack the polybasic cleavage sites. To sum up, there possibly was an intermediate host between the virus and human transmission and although there are similarities in between bat corona virus and the current SARS-CoV-2; nothing can be asserted with certainty. A point to note would also be that we are genetically identical to Chimpanzees by 99% (Ebersberger et al., 2002), to Orangutans by 97% and to Gorillas by 98.4%. The 96% genetic similarity between SARS-CoV-2 and RatG13 may sound pretty similar but this is still a lot of genetic variation and some studies have proven that they separated 40-70 years ago.

Human body reaction– What possibly happens when a virus enters human body? When the viruses which were previously subjected to a very efficient immune system of bats get a much weaker host (humans), they begin rapid multiplication. The immune system of human body could in turn over-react and produce excessive or uncontrolled levels of cytokines (cytokine storm), resulting in hyper-inflammation and this reaction could seriously harm a patient.

Why are bats important– We always seem to forget that we’ve been coexisting with bats for millions of years. They probably are in the crevices and under-roofs of your house, and at night they are feeding on crop pests in the agricultural fields nearby. Bats have been providing an amazing scale of ecosystem services- pollination, seed dispersal, insect pest suppression, their guano used as fertilizers, and they are environmental indicators. Instead of blaming these species, it is very significant to study their ecology, immunology and physiology. The solutions to the current pandemic and many other inflammation related diseases (heart attacks, cancer) lie in studying them. Culling bats to prevent this current situation is the worst measure. It is these type of activities coupled with habitat loss that, in the first hand, started this situation. There are diseases everywhere, from your body to your bed, from your phone to your water bottle. This doesn’t mean that you burn yourself and your house to become disease-free.

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Picture- A Maternity aggregation of Intermediate Horseshoe bat (R. affinis). Picture- Sanjeev Baniya

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References

1) Andersen, K.G., Rambaut, A., Lipkin, W.I., Holmes, E.C. and Garry, R.F., 2020. The proximal origin of SARS-CoV-2. Nature Medicine, pp.1-3.

2) Baker, M.L., Schountz, T. and Wang, L.F., 2013. Antiviral immune responses of bats: a review. Zoonoses and public health60(1), pp.104-116.

3) Burgin, Connor J., et al. “How many species of mammals are there?” Journal of Mammalogy 99.1 (2018): 1-14.

4) Canale, C.I. and Henry, P.Y., 2011. Energetic costs of the immune response and torpor use in a primate. Functional Ecology25(3), pp.557-565.

5) Ebersberger, I., Metzler, D., Schwarz, C. and Pääbo, S., 2002. Genomewide comparison of DNA sequences between humans and chimpanzees. The American Journal of Human Genetics70(6), pp.1490-1497.

6) O’shea, Thomas J., Paul M. Cryan, Andrew A. Cunningham, Anthony R. Fooks, David TS Hayman, Angela D. Luis, Alison J. Peel, Raina K. Plowright, and James LN Wood. “Bat flight and zoonotic viruses.” Emerging infectious diseases 20, no. 5 (2014): 741.

7) Zhang, G., Cowled, C., Shi, Z., Huang, Z., Bishop-Lilly, K.A., Fang, X., Wynne, J.W., Xiong, Z., Baker, M.L., Zhao, W. and Tachedjian, M., 2013. Comparative analysis of bat genomes provides insight into the evolution of flight and immunity. Science339(6118), pp.456-460.

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