Air Pollution Causes Increased Covid-19 Severity
Research group at Kyoto University unravels part of the mechanism
PM2.5 enhances the cell infection route for SARS-CoV-2

Air pollution is helping to spread Covid-19. A research group at Kyoto University, including Professor Hirohisa Takano of the Graduate School of Global Environmental Studies, and Tomoya Sagawa of the Graduate School of Engineering, and other students has shown that when mice are exposed to PM 2.5 and PM 10 collected from the air in Japanese cities, the quantity of ACE2 proteins and TMPRSS2 enzymes in their type II pneumocytes increases by several dozen times. Takano explains, "The quantity used for exposure was very high, so the mechanism is not believed to have a significant impact with the air in Japan, but in some regions such as South East Asia, it will be necessary to administer medicines that have the effect of limiting TMPRSS2 as a preventive measure." The results were published in Environmental Research.

It has been suggested in various locations throughout the world that air pollution, caused by particulate matter such as PM 2.5 and PM 10, causes an increase in the number of Covid-19 infections and the number of serious cases. It was reported in Wuhan, China, that two days after a high recorded level of PM 2.5 and PM 10, the Covid-19 fatality rate increased. It has also been reported that the Covid-19 death rate was correlated with the 17-year average PM 2.5 level in the US. However, until now there were no papers published providing experimental evidence of the effect of PM (particulate matter in the air) in worsening Covid-19.

PM 2.5 is generally assumed to cause inflammation when it enters the respiratory system due to the innate immune response. It can trigger such ailments as allergies, bronchial asthma, respiratory inflammation, bronchitis, and pneumonia. It was believed that Covid-19 also became more severe via the same mechanism, but Takano believed there were other influences as well.

To examine the possibility, group gathered PM from the air in cities throughout Japan using the cyclone methodology developed by Professor Tomoaki Okuda of the Keio University Faculty of Science and Technology. They then separated the PM from the air into PM 2.5 particles, including those actually smaller than 2.5 nm, and PM 10 particles, including those 5 to 10 nm in size, and inserted 500 micrograms into the respiratory systems of mice. Then they examined lung slices from the mice one day after application using multiple immunostainings to investigate the location and quantity of ACE2 and TMPRSS2 and found that both had increased compared to the control group. Specifically, they found, for the first time in the world, that both had increased in type II pneumocytes by several dozen times compared to the control group. There was no difference between the effects of PM 2.5 and PM 10, and ACE2 and TMPRSS2 were not increased due to the inflammatory reaction.

SARS-CoV-2 infects cells by binding with the ACE2 membrane protein on the surface of cells after which the enzyme TMPRSS2 brings the viral RNA inside the cell. Takano explains, "PM in a sense widens the doorway for SARS-CoV-2 by increasing ACE2 and TMPRSS2. In particular, it is possible that the onset and severity of Covid-19 is brought about through the creation of surfactants to widen the path of infection to type II pneumocytes, which are important for maintaining pulmonary stretching."

He explains further that the experiment involved a high quantity of PM, so the observed effect does not likely occur within Japan where the air is cleaner, but it is related to the acute worsening of Covid-19 that occurred in Wuhan. Therefore, areas with high PM contamination should require environmental measures in addition to medical measures. The group suggests the administration of Bromhexine, Camostat, and Nafamostat, which have been confirmed to control TMPRSS2, as a preventive measure may be effective.

The research group is continuing to examine the question of which particles and substances, of the many found in the environment, are related to the onset and worsening of Covid-19, and what medicines there may be to prevent or limit that effect.