COVID-19 and PM2.5 Sodium Chloride content

INTRODUCTION: Following national lockdown instituting physical distancing, COVID-19 infection and mortality decreased in most countries. Simultaneously due to diminished economic and human activity, the atmospheric levels of PM2.5, an important airborne pollutant, decreased significantly. COVID-19 has been found adherent to PM2.5. PM2.5 has various components including sodium chloride which determines the amount of PM2.5 salt-derived water content. Atmospheric salt content in part determines the sodium chloride content and the consequential hygroscopicity of PM2.5. COVID-19 possesses a C-terminal protein which is hydrophobic. METHOD: The sodium chloride content of the PM2.5 species was assessed in two groups of cities. Cities were chosen as opposed to countries, because substantial regional differences in infection rates were noted between inland and coastal cities. These cities were differentiated by the rate COVID-19 infection and consequent mortality. Atmospheric salt content was obtained from research that assessed chloride ion wet deposition, a proxy for airborne salinity. The salt content of the relevant PM2.5 species was obtained from publications from the various cities assessed. RESULTS: Cities with high COVID-19 infection rates had PM2.5 species with significantly lower salt content than the cities with low Covid-17 infection. The PM2.5 salt content in the cities with elevated COVID-19 rates was 0.196µg/m 3 SD 0.05µg/m 3 , while cities with low COVID-19 rates had a PM2.5 salt content of 0.81µg/m 3 SD 0.32µg/m 3 (p<0.0001). mgCl/m 2 /day) compared to sodium chloride levels noted in cities with high COVID-19 rates of infection (40-125. mgCl/m 2 /day) (p<0.005). CONCLUSION: PM2.5 with low salt content, in the presence of low ambient salinity may be linked to an increased risk of COVID-19 infection in the population.


INTRODUCTION
COVID-19 infection appears to be decreasing in most countries. This decrease is attributed to the social distancing legally enforced in most countries. Concomitant with the reduction in COVID-19 infection incidence, a significant decrease in pollution, including PM2.5 levels, were noted 1,2,3 . A significant reduction in COVID-19 related mortality was also noted in relation to a reduction in PM2.5 4 There are some countries and cities which appear to have contained the infection prior and after lockdown, including Malta, Hong Kong, Cyprus, South Korea, Australia, New Zealand and Taiwan 5,6 . There are factors in common to the countries which appear to have contained the COVID-19 pandemic. Geographical isolation, whereby most of these countries are in fact islands, may have prevented large population movements which encourage mass spread of infection -physical distancing on a national scale. Legal implementation of social distancing in small isolated populations may be easier to enforce. Legislation enforcing public health measures such as physical distancing and procedures to protect the elderly and vulnerable individuals may be more effective 7 .
Concomitant with social distancing a reduction in human mobility and economic activity resulted. The reduction in activity in turn led to significant diminution in pollution including PM2.5 levels 1,2,3 . There lies the possibility that besides, the undoubtedly effective measures of physical distancing at reducing viral transmission, there may be environmental factors including the level and composition of the pollutant PM2.5 that may impact COVID-19 infection.
COVID-19 has been found adherent to PM2.5 8 . Atmospheric salinity determines the PM2.5's sodium chloride component which in turn determines the water content of PM2.5 9 . The C-terminal of a viral fusion peptide is strongly hydrophobic 10,11 and the water content of PM2.5 may act as a deterrent to COVID-19 adhesion to this particulate matter.

METHODOLOGY
The salt content of particulate matter PM2.5 and atmospheric salt content were assessed from a number of cities, differentially affected by COVID-19 infection. Cities were selected as opposed to countries, because substantial regional differences in infection rates have noted especially between inland and coastal cities 12 . The cities chosen to be assessed were divided into two groups. The first group (Group 1) included Wuhan, Qom, Bergamo, Madrid, New York, Limburg (Vredepeel), Atlanta, and Pretoria, all having significantly high rates of COVID-19 infection, compared to other cities in their respective countries. Group 2 consisted of cities including Seoul, Hanoi, Rehovot, Buenos Aires, Singapore, Beijing, Kanpur, Dhaka, Taipei, Rotterdam, Hong Kong and Malta, all of which have very low rates of COVID-19 infection 12 . An important caveat is that infection and mortality rates very much depend on the level of COVID-19 testing in the individual populations.
The level of atmospheric salt content may be inferred from the chloride ion wet deposition index measured as mgCl/m 2 /day. Atmospheric salt content levels were obtained from an indexed colour coded map compiled by Fraunhofer ISE, through a site set up by the Galvanizers Association 13 . This map determines the level of salt content in different regions in the world in connection with the risk of automobile corrosion. The data are represented as maximum and minimum levels per day .

RESULTS
There was a significant difference in the salt content of PM2.5 between both groups of cities. Cities with low COVID-19 infection rates had significantly higher salt content in the PM2.5, compared to the cities with high levels of COVID-19 infection. The PM2.5 salt content in the cities with high COVID-19 rates was 0.196µg/m 3 SD +/-0.05µg/m 3 , while cities with low COVID-19 infection rates had a PM2.5 salt content of 0.81µg/m 3 SD +/-0.32µg/m 3 (p<0.0001). The cities that seem to have contained the pandemic are close or surrounded by sea, and consequently have an elevated atmospheric salt content. Cities that evaded high COVID-19 infection rates have higher atmospheric salt content levels, minimum/maximum 216-1080 mgCl/m 2 /day compared to minimum/maximum 40-125 mgCl/m 2 /day (p<0.005) noted in cities sustaining high COVID-19 rates of infection. Normality plots applied to the PM2.5 salt content showed parametric patterns allowing the application of the T-Test. Both the maximum and minimum atmospheric salt content levels were nonparametric whereby the Mann -Whitney U test was applied. Spearman Rank test was applied to assess statistical correlations to nonparametric variables.
The results are demonstrated in two tables designated Figure 1. and Figure 2.  23 . In India, reductions of the order of 43% and 31% were noted for PM2.5 and PM10 respectively, during lockdown period compared to previous years. During the same period carbon monoxide decreased by 10% and nitrous oxide decreased by 18%. The air quality index (AQI) improved throughout India following lockdown 24 .
Before statutory lockdown, there may have been synergism between high PM2.5 levels and COVID-19 in infection transmission. This synergism may have also determined the severity of COVID-19 sequelae. Pathological synergism between PM2.5 and respiratory infection has been shown in animal studies. Preclinical studies, exposing mice to cigarette smoke demonstrated that following intratracheal injection of streptococcus pneumoniae, bacterial counts in murine lungs were higher than the control group 25 . Another study showed that air pollution could result in dysfunction of rat tracheal cilia, causing mucus stasis and resultant infection. Moreover a declined nonspecific immune defense, was noted making the rats more prone to secondary infection 26 . Viability and phagocytic activity of alveolar macrophages decreased significantly following the instillation of PM2.5 particles in Wistar rats 27,28 .
Similar deleterious effects of PM2.5 have been found in the respiratory system of humans. PM2.5 releases free radicals, metal and the organic components inducing free radical production leading to oxidation of lung tissue 29 . Through PM2.5's propensity to produce free radicals, peroxidation of lipids on the cell membrane occurs, with consequent elevation of intracellular calcium. High levels of intracellular calcium increases inflammatory cytokine production (Kim et al 1997). PM2.5induced inflammation led to an increase in the number of neutrophils, eosinophils, T cells and mastocytes 30.31 . All these cells can result in inflammatory cytokine production and resultant cytokine storm has been responsible for a significant number of COVID-19 related deaths 32 Addressing this synergism may protect the populations from airborne infections such as the COVID-19 infection and simultaneously foster respiratory health. Prior to the outbreak of COVID-19 in Wuhan, Qom and Bergamo the Air Quality Index demonstrated strikingly elevated pollution levels of PM2.5 33 . These elevated levels of PM2.5 occurred during the winter months possibly due to combustion of fuel for residential heating purposes.
Inferring from the fact that coastal cities have been in the main been spared from high COVID-19 infection, another environmental factor may come into play in the form of the level of atmospheric salt content. Chloride ion wet deposition, a variable reflecting the ambient salinity could be obtained from a colour-coded map of the distribution of the earth's salt content. 13 Wuhan has been noted to be one of the cities in China with the least salt content in the air 14 . The cities hard hit by COVID-19 infection are distant from the sea and consequently have low salt content levels [14][15][16][17][18][19][20][21][22]  Healthy levels of airway salt content protect the respiratory system disease. Hypertonic saline has been shown to have anti-infective properties 34 . Tracheobronchial ciliary action is accentuated when the saline content of the endobronchial tree is optimal. Optimal levels of tracheal sodium chloride are mucolytic making bronchial mucus is less viscous with. Patients with respiratory condition such as asthma and cystic fibrosis benefit from endo-bronchially nebulized saline 35 A protein component of COVID-19 virus is hydrophobic 10,11 . Viral cell entry is mediated through extensive post-receptor-binding structural readjustments on the cell membrane. The hydrophobic peptides include the C-terminal of a fusion peptide 11,12 . Low concentrations of chlorinated solutions are lethal to the virus 37 . Atmospheric salt content may be another environmental factor that may have protected some populations preventing airborne infection from the COVID-19.
Variable amounts of sodium chloride are found on PM2.5 species 9 . The PM2.5 species vary from city to city, and there are also seasonal changes in the sea salt component of the PM2.5. As a corollary to the variable amount of PM2.5 sodium chloride component, there also a variable degree of hygroscopicity related to the sea salt-derived water content 9 . Besides the lethal effect of sodium chloride on the virus, there may be a connection with aerosol adhesion due to sodium chloride with the pollutant PM2.5. Recent evidence suggests that COVID-19 may adhere to PM2.5 particles to evade the bronchial tree defences and colonize the alveoli 8 . The presence of hygroscopic sodium chloride on PM2.5 may act as a deterrent against the adhesion of the hydrophobic proteins of COVID-19 to these particles, protecting populations living in regions with salt-rich PM2.5 prevalent high salt content regions.
CONCLUSION: The COVID-19 pandemic may have occurred due to the combination of a number of environmental factors besides the virulence of the virus. A decrease in airborne pollution in particular PM2.5 and possibly the sodium chloride rich species of PM2.5 may have protected some populations from the COVID-19 pandemic.