Assembling an Anti-COVID-19 Artillery in the Battle against the New Coronavirus

*Chanda Siddoo-Atwal*

## **Abstract**

The panic and confusion surrounding the pandemic caused by the novel coronavirus requires a systematic study of the disease (COVID-19) and the arsenal of weapons available to the biochemist in the fight against infection. When developing a particularly bad flu in January 2020 while in India after the visit of a friend, who had just travelled back from Wuhan (China), it gave me an early opportunity to study the tricky diagnosis of this dreaded disease first-hand. The somewhat unusual symptoms and a lingering weakness and malaise for months suggested that it was no ordinary influenza virus. Since that time, a baffling number of disparate symptoms have been ascribed to COVID-19 infection including respiratory, gastrointestinal, circulatory, urinary tract and nerve dysfunction that have even resulted in multi-organ failure in some cases. Naturally, an array of risk factors have also been identified ranging from age, sex, obesity, diabetes, and hypertension to cigarette smoking that can increase mortality rate dramatically. In the intervening period, much research has appeared on biochemical compounds that may help to prevent this infection and, possibly, aid in patient recovery. Among these bioactive molecules are certain anti-inflammatory substances such as vitamin D, zinc, chloroquine, soy isoflavones like genistein, and glycyrrhizic acid, some of which may be successful in attacking different biochemical processes of the new coronavirus and disarming its deadly artillery against the human host. In a few instances, the viral processes that are inhibited by these chemicals are essential for the replication and reproduction of this RNA virus thereby striking a lethal blow to its machinery. Thus, taken together, these compounds may form a worthy arsenal against a formidable foe in the absence of an effective vaccine, and, especially, if relapse or re-infection proves to be a common occurrence in recovered COVID-19 patients.

**Keywords:** novel coronavirus, COVID-19, influenza, obesity, diabetes, hypertension, cigarette smoke, vitamin D, zinc, chloroquine/quinine, soy isoflavones, genistein, glycyrrhizic acid, RNA virus replication

#### **1. Life cycle of the novel coronavirus**

Coronaviruses are large, enveloped, single-stranded, positive-sense RNA viruses with a genome of approximately 30 kilobases in length. The genus *Coronavirus* belongs to the family *Coronaviridae* in the order *Nidovirales*. They are classified into three groups. Group 1 contains various mammalian viruses including porcine epidemic diarrhea virus, porcine transmissible gastroenteritis virus, and human coronaviruses 229E and NL63. Group 2 includes canine respiratory coronavirus

among other mammalian viruses and human coronavirus OC43. Human severe acute respiratory syndrome coronavirus (SARS-CoV-1) is considered a distant relative of this group. Group 3 contains solely avian coronaviruses. Human coronaviruses (HCoVs) cause respiratory infections, mainly, but gastroenteritis and neurological disorders may also occur. So far, at least seven human coronaviruses have been described including SARS-CoV-2, which was just sequenced in 2020, and two of these coronaviruses (OC43 and 229E) are responsible for 10–30% of all common colds. HCoV-HKU1 is mostly associated with bronchiolitis and pneumonia [1–3].

The gross life cycle of the SARS-CoV-1 has been observed in Vero E6 cells (African green monkey kidney cells) following inoculation with the virus under an electron microscope. The SARS-CoV-1 enters the cells through membrane fusion. Then, the nucleocapsids are assembled in the rough endoplasmic reticulum (RER) and mature by budding into the smoothe vesicles derived from the Golgi apparatus. Finally, the smoothe vesicles fuse with the cell membrane and the mature virus particles are released [4]. SARS-CoV-2 displays a similar life cycle.

Recent molecular studies have revealed that in order to facilitate entry of the virus into a human cell, the "S" spike surface glycoprotein of SARS-CoV-2 binds to the angiotensin-converting enzyme 2 (ACE-2) cellular receptor. Binding of the virus occurs via the S1 subunit of the S protein to a receptor and entry requires S protein priming by the cellular serine protease in order to allow fusing together of viral and cell membranes, a process which is initiated by the S2 subunit [5]. Following the fusion of viral and plasma membranes, the virus RNA undergoes transcription and replication inside the cell cytoplasm. Viral proteins are synthesized and the new RNA genomes are assembled and packaged in the endoplasmic reticulum, in the Golgi apparatus, and in the endoplasmic reticulum-Golgi intermediate compartment prior to virion release in vesicles. In fact, the S protein of SARS-CoV-2 binds to ACE-2 receptors with an approximately 10–20 fold higher affinity than that of SARS-CoV-1 and this added feature may aid in the efficient spread of SARS-CoV-2 among human populations. However, SARS-CoV-2 does not employ the other usual CoV receptors such as aminopeptidase N and dipeptidyl peptidase 4 to enter human cells [6].

ACE-2 is a membrane-associated aminopeptidase that converts angiotensin II to angiotensin 1–7 and plays a role in the cleavage of peptides [3]. Expression of ACE-2 in human tissues correlates with known sites of SARS-CoV-1 infection including lungs (particularly airway epithelia), heart, kidneys, small intestine, testes, and vascular endothelia [7]. These same tissues also overlap with the sites of SARS-CoV-2 infection in humans due to ACE-2 receptor availability.

#### **2. A personal experience**

On a personal note, as a biochemist, I have been following every bit of new research on any chemical compound that might successfully combat the virus. Around January 6th, 2020, I developed a very bad flu while in India after meeting with a friend who had just travelled to Wuhan in China. Overnight, I got a sorethroat that lasted a few days followed by a severe head cold with sinus congestion and mucous and, finally, it developed into a dry cough. During this debilitating flu, I also had some loose bowel movements with mucous. In the aftermath of the flu that lasted around 14 days, I was plagued with dizziness and weakness for two more weeks.

Although we had heard of the novel coronavirus in China, there was no reason to believe that was what I had just experienced since there had been no unusual respiratory distress. So, it did not seem to overlap with the pneumonia-like symptoms of the new coronavirus from China. Moreover, the friend had returned at the beginning of January and, as far as we knew at that time, the virus had only appeared in

**11**

*Assembling an Anti-COVID-19 Artillery in the Battle against the New Coronavirus*

December. Therefore, it seemed unlikely that the friend had been exposed to any infected individuals while in China. Furthermore, the traveller from China never became sick (although one other person who attended the same meeting as myself developed a very bad flu within two weeks of coming in contact with this person). At the same time, there are also many seasonal flus like swine flu (H1N1) that are endemic in India, so there was no reason to consider that it was a coronavirus infection. Finally, the only medicines I took initially were some herbal Ayurvedic cold remedies mainly with a licorice-root base (a potent anti-inflammatory), aspirin at night, and an electrolyte solution to prevent dehydration from diarrhea. When I had a relapse of the gastrointestinal symptoms in March including stomach pain after I returned to Canada, a course of azithromycin helped to resolve the symptoms.

However, it was only when the weakness and malaise persisted for 3–4 months after the initial illness and new data started to emerge about the differing patterns of COVID-19 infection, that I started to consider another possible cause. Firstly, all my symptoms were consistent with the disparate effects of the novel coronavirus including the lingering apathy. Secondly, it became apparent that the new coronavirus had appeared in Wuhan some time before December. Thirdly, unlike other flu viruses, the phenomenon of asymptomatic spreaders became widely known. So, now, even though I had not been tested for the new virus or COVID-19 antibodies, I started to suspect that I could have experienced a form of coronavirus infection. Finally, I had my COVID-19 test in August 2020 and, although it was negative, it did not preclude the possibility that I had the disease in January 2020 and that my body had formed and shed antibodies to the novel coronavirus (antibody testing was also negative). Since it is not known exactly how long antibodies persist following infection, even these may not be detected after a certain recovery period (there are recent reports antibodies decline after three months). Studies in rhesus monkeys show that re-infection does not occur in the recovered macaques up to 28 days after initial infection [8]. Nevertheless, prolonged inflammation and reports of re-infection in recovered humans are a surprising aspect of this virus. In my case, one additional negative C-reactive protein (inflammatory marker) test decisively clinched the matter.

Some scientists have opined that COVID-19 is highly contagious and highly lethal to a small subset of the population, while it produces milder symptoms in most people. Although the SARS-CoV-2 virus infects people of all ages, the World Health Organization (WHO) has determined that the evidence to date suggests that older adults and adults with underlying medical conditions are at a higher risk of

One large study out of New York State seems to indicate that obesity, high blood pressure, and diabetes are strong risk factors for COVID-19 [10]. It has also been observed that cardiovascular disease and respiratory diseases could greatly affect the prognosis [11]. In fact, in an interesting German study involving autopsies on 12 COVID-19 patients the results revealed that coronary heart disease and asthma

Other research suggests that cancer patients are more vulnerable to COVID-19 infection. A multicenter study showed that patients with cancer had higher risks in all severe outcomes of the disease tested. Hematologic cancer, lung cancer, or metastatic cancer (stage IV) cases experienced the highest frequency of severe events, while nonmetastatic cancer cases experienced similar frequencies to patients without

were common comorbid conditions in 50% of the deceased [12].

*DOI: http://dx.doi.org/10.5772/intechopen.95100*

**3. Top COVID-19 risk factors**

developing severe COVID-19 disease [9].

**3.1 Internal risk factors**

#### *Assembling an Anti-COVID-19 Artillery in the Battle against the New Coronavirus DOI: http://dx.doi.org/10.5772/intechopen.95100*

December. Therefore, it seemed unlikely that the friend had been exposed to any infected individuals while in China. Furthermore, the traveller from China never became sick (although one other person who attended the same meeting as myself developed a very bad flu within two weeks of coming in contact with this person). At the same time, there are also many seasonal flus like swine flu (H1N1) that are endemic in India, so there was no reason to consider that it was a coronavirus infection. Finally, the only medicines I took initially were some herbal Ayurvedic cold remedies mainly with a licorice-root base (a potent anti-inflammatory), aspirin at night, and an electrolyte solution to prevent dehydration from diarrhea. When I had a relapse of the gastrointestinal symptoms in March including stomach pain after I returned to Canada, a course of azithromycin helped to resolve the symptoms.

However, it was only when the weakness and malaise persisted for 3–4 months after the initial illness and new data started to emerge about the differing patterns of COVID-19 infection, that I started to consider another possible cause. Firstly, all my symptoms were consistent with the disparate effects of the novel coronavirus including the lingering apathy. Secondly, it became apparent that the new coronavirus had appeared in Wuhan some time before December. Thirdly, unlike other flu viruses, the phenomenon of asymptomatic spreaders became widely known. So, now, even though I had not been tested for the new virus or COVID-19 antibodies, I started to suspect that I could have experienced a form of coronavirus infection.

Finally, I had my COVID-19 test in August 2020 and, although it was negative, it did not preclude the possibility that I had the disease in January 2020 and that my body had formed and shed antibodies to the novel coronavirus (antibody testing was also negative). Since it is not known exactly how long antibodies persist following infection, even these may not be detected after a certain recovery period (there are recent reports antibodies decline after three months). Studies in rhesus monkeys show that re-infection does not occur in the recovered macaques up to 28 days after initial infection [8]. Nevertheless, prolonged inflammation and reports of re-infection in recovered humans are a surprising aspect of this virus. In my case, one additional negative C-reactive protein (inflammatory marker) test decisively clinched the matter.

## **3. Top COVID-19 risk factors**

#### **3.1 Internal risk factors**

*Some RNA Viruses*

among other mammalian viruses and human coronavirus OC43. Human severe acute respiratory syndrome coronavirus (SARS-CoV-1) is considered a distant relative of this group. Group 3 contains solely avian coronaviruses. Human coronaviruses (HCoVs) cause respiratory infections, mainly, but gastroenteritis and neurological disorders may also occur. So far, at least seven human coronaviruses have been described including SARS-CoV-2, which was just sequenced in 2020, and two of these coronaviruses (OC43 and 229E) are responsible for 10–30% of all common colds. HCoV-HKU1 is mostly associated with bronchiolitis and pneumonia [1–3]. The gross life cycle of the SARS-CoV-1 has been observed in Vero E6 cells (African green monkey kidney cells) following inoculation with the virus under an electron microscope. The SARS-CoV-1 enters the cells through membrane fusion. Then, the nucleocapsids are assembled in the rough endoplasmic reticulum (RER) and mature by budding into the smoothe vesicles derived from the Golgi apparatus. Finally, the smoothe vesicles fuse with the cell membrane and the mature virus

particles are released [4]. SARS-CoV-2 displays a similar life cycle.

SARS-CoV-2 infection in humans due to ACE-2 receptor availability.

On a personal note, as a biochemist, I have been following every bit of new research on any chemical compound that might successfully combat the virus. Around January 6th, 2020, I developed a very bad flu while in India after meeting with a friend who had just travelled to Wuhan in China. Overnight, I got a sorethroat that lasted a few days followed by a severe head cold with sinus congestion and mucous and, finally, it developed into a dry cough. During this debilitating flu, I also had some loose bowel movements with mucous. In the aftermath of the flu that lasted around 14 days, I was plagued with dizziness and weakness for two more weeks.

Although we had heard of the novel coronavirus in China, there was no reason to believe that was what I had just experienced since there had been no unusual respiratory distress. So, it did not seem to overlap with the pneumonia-like symptoms of the new coronavirus from China. Moreover, the friend had returned at the beginning of January and, as far as we knew at that time, the virus had only appeared in

**2. A personal experience**

Recent molecular studies have revealed that in order to facilitate entry of the virus into a human cell, the "S" spike surface glycoprotein of SARS-CoV-2 binds to the angiotensin-converting enzyme 2 (ACE-2) cellular receptor. Binding of the virus occurs via the S1 subunit of the S protein to a receptor and entry requires S protein priming by the cellular serine protease in order to allow fusing together of viral and cell membranes, a process which is initiated by the S2 subunit [5]. Following the fusion of viral and plasma membranes, the virus RNA undergoes transcription and replication inside the cell cytoplasm. Viral proteins are synthesized and the new RNA genomes are assembled and packaged in the endoplasmic reticulum, in the Golgi apparatus, and in the endoplasmic reticulum-Golgi intermediate compartment prior to virion release in vesicles. In fact, the S protein of SARS-CoV-2 binds to ACE-2 receptors with an approximately 10–20 fold higher affinity than that of SARS-CoV-1 and this added feature may aid in the efficient spread of SARS-CoV-2 among human populations. However, SARS-CoV-2 does not employ the other usual CoV receptors such as aminopeptidase N and dipeptidyl peptidase 4 to enter human cells [6]. ACE-2 is a membrane-associated aminopeptidase that converts angiotensin II to angiotensin 1–7 and plays a role in the cleavage of peptides [3]. Expression of ACE-2 in human tissues correlates with known sites of SARS-CoV-1 infection including lungs (particularly airway epithelia), heart, kidneys, small intestine, testes, and vascular endothelia [7]. These same tissues also overlap with the sites of

**10**

Some scientists have opined that COVID-19 is highly contagious and highly lethal to a small subset of the population, while it produces milder symptoms in most people. Although the SARS-CoV-2 virus infects people of all ages, the World Health Organization (WHO) has determined that the evidence to date suggests that older adults and adults with underlying medical conditions are at a higher risk of developing severe COVID-19 disease [9].

One large study out of New York State seems to indicate that obesity, high blood pressure, and diabetes are strong risk factors for COVID-19 [10]. It has also been observed that cardiovascular disease and respiratory diseases could greatly affect the prognosis [11]. In fact, in an interesting German study involving autopsies on 12 COVID-19 patients the results revealed that coronary heart disease and asthma were common comorbid conditions in 50% of the deceased [12].

Other research suggests that cancer patients are more vulnerable to COVID-19 infection. A multicenter study showed that patients with cancer had higher risks in all severe outcomes of the disease tested. Hematologic cancer, lung cancer, or metastatic cancer (stage IV) cases experienced the highest frequency of severe events, while nonmetastatic cancer cases experienced similar frequencies to patients without cancer. Moreover, cancer patients who received surgery had higher risks of severe events than patients without cancer or those who underwent radiotherapy [13].

In addition, a surprising gender disparity appears to be present in relation to SARS-CoV-2 infection. Statistics from Australia, Belgium, Germany, Italy, the Netherlands, South Korea, Spain, the U.K and the US reveal that mortality rates from the virus are significantly higher in infected males than in infected females. In New York, approximately 60% of COVID-19-related deaths occurred in men. This may partly reflect biological characteristics since women produce stronger immune responses than men and are physically better at warding off viral and other types of infections. Nevertheless, biochemical differences in sex hormones are also likely to play a role in determining this dichotomy [14] and certain researchers have suggested it may be due to the presence of ACE-2 receptors in the testicles [15].

In the largest Chinese study to date assessing severity of coronavirus infection in smokers, it was found that higher percentages of current and former smokers needed ICU support or mechanical ventilation. Higher percentages of smokers among the severe cases also died [16]. Therefore, ultimately, the risk of any one individual is determined by the number of risk factors they display. For example, a ninety year old male smoker with diabetes and hypertension displaying five risk factors (age, gender, smoke inhalation, high blood pressure, and diabetes) would have an extremely high risk of contracting a terminal case of COVID-19.

However, genetic risk factors as a result of ethnic origin can only be considered once all these other significant risk factors have been taken into consideration. So far, despite attempts by various institutions to prove an ethnic link to COVID-19 infection, there is no compelling evidence to suggest that any one human group is genetically more susceptible to the novel coronavirus than any other beyond mitigating factors such as socioeconomic status or environmental conditions [17]. In order to establish a true genetic component, rigorous genetic testing must be undertaken to identify predisposing genes in susceptible ethnic groups. Prior to gene isolation and identification of a specific genetic polymorphism, a biochemical reaction resulting in a higher percentage of the disease is often demonstrated in a particular human population. As an example, the human sunburn cycle in response to UVA/B radiation only occurs in a minority of people with fair skin; however, most people simply tan when they are exposed to sunlight. In fact, these represent two separate physiological processes (burning and tanning). The former condition, scientific sunburn as a result of the human sunburn cycle, is mostly due to a genetic polymorphism involving the expression of very low levels of melanin in human skin since it can be corrected by wearing a sunscreen containing black sesame melanin [50 mg/ml] in a zinc oxide cream base [7.5%] [18–20]. It is also correlated with a high risk for skin cancer. Nonetheless, there may be other genetic factors like differences in DNA repair enzyme activity which can contribute to this unusual trait in certain individuals, as well [21].

Simultaneously, a surprising recent genetic association study has revealed that a major genetic risk factor for severe COVID-19 in humans may actually be inherited from Neanderthals. Outside the continent of Africa (0.3%), modern humans have inherited significantly more genetic material from other hominid species including Neanderthals (approximately 2%) and Denisovans [22]. Europeans and South Asians appear to have the greatest complement of Vindija Neanderthal genes from Croatia and a gene cluster on chromosome 3 inherited from this species has been identified as a risk locus for respiratory failure after infection with SARS-CoV-2. Among certain South Asian populations, up to 50% can carry at least one copy of this risk haplotype and the highest carrier frequency occurs in Bangladesh where 63% of the population carries it. In the UK it has been reported that individuals of Bangladeshi origin have roughly a two times higher risk of dying from COVID-19 than people of other nationalities [23].

**13**

*Assembling an Anti-COVID-19 Artillery in the Battle against the New Coronavirus*

Interestingly, there are high levels of air pollution in the two regions of China and Northern Italy that were hardest hit by the virus suggesting that environmental conditions can have an impact on the infectiousness of the disease [24]. Italian researchers have recently proposed an association between higher mortality rates in Northern Italy and peaks of particulate matter concentrations in this region. The most polluted northern provinces of Italy were found to have more infection cases than the less polluted southern provinces and this correlated well with ambient particulate matter concentrations that often exceeded the legal limit in these areas. All data for this study was collected prior to the lockdown [25]. Surprisingly, further research by the same group demonstrated that SARS-CoV-2 RNA was present on outdoor airborne particulate matter that was collected from an industrial site in Bergamo, Italy. This evidence suggests that, under the right atmospheric conditions, SARS-CoV-2 could create clusters with particulate matter and enhance persistence of the virus in the atmosphere by facilitating its capacity for diffusion. However, the vitality and virulence of the coronavirus diffused via this method remain to be

This could have been a significant factor in the spread of the coronavirus in highly polluted and populated cities like Mumbai, India. Social conditions such as crowding in slums have also been considered contributory to dispersal of the virus in developing countries like Brazil and India. Proximity to infected individuals increases the risk of person-to-person transmission since the SARS-CoV-2 virus is

No matter how healthy an individual may be, the more exposure they have to a particular virus, the greater risk they have of contracting the disease. The greater the number of particles of the virus one is exposed to, the greater the chance that they will overwhelm the body and immune responses. This is the reason that young doctors and other frontline healthcare workers are getting serious cases of

**View of Downtown Mumbai – December 2019**

spread mainly by respiratory droplets, but can be aerosolized, too [3].

COVID-19 and dying at a higher frequency than the general population.

*DOI: http://dx.doi.org/10.5772/intechopen.95100*

**3.2 External risk factors**

confirmed [26].

*Assembling an Anti-COVID-19 Artillery in the Battle against the New Coronavirus DOI: http://dx.doi.org/10.5772/intechopen.95100*

### **3.2 External risk factors**

*Some RNA Viruses*

cancer. Moreover, cancer patients who received surgery had higher risks of severe events than patients without cancer or those who underwent radiotherapy [13]. In addition, a surprising gender disparity appears to be present in relation to SARS-CoV-2 infection. Statistics from Australia, Belgium, Germany, Italy, the Netherlands, South Korea, Spain, the U.K and the US reveal that mortality rates from the virus are significantly higher in infected males than in infected females. In New York, approximately 60% of COVID-19-related deaths occurred in men. This may partly reflect biological characteristics since women produce stronger immune responses than men and are physically better at warding off viral and other types of infections. Nevertheless, biochemical differences in sex hormones are also likely to play a role in determining this dichotomy [14] and certain researchers have suggested it may be due to the presence of ACE-2 receptors in the testicles [15].

In the largest Chinese study to date assessing severity of coronavirus infection in smokers, it was found that higher percentages of current and former smokers needed ICU support or mechanical ventilation. Higher percentages of smokers among the severe cases also died [16]. Therefore, ultimately, the risk of any one individual is determined by the number of risk factors they display. For example, a ninety year old male smoker with diabetes and hypertension displaying five risk factors (age, gender, smoke inhalation, high blood pressure, and diabetes) would

However, genetic risk factors as a result of ethnic origin can only be considered once all these other significant risk factors have been taken into consideration. So far, despite attempts by various institutions to prove an ethnic link to COVID-19 infection, there is no compelling evidence to suggest that any one human group is genetically more susceptible to the novel coronavirus than any other beyond mitigating factors such as socioeconomic status or environmental conditions [17]. In order to establish a true genetic component, rigorous genetic testing must be undertaken to identify predisposing genes in susceptible ethnic groups. Prior to gene isolation and identification of a specific genetic polymorphism, a biochemical reaction resulting in a higher percentage of the disease is often demonstrated in a particular human population. As an example, the human sunburn cycle in response to UVA/B radiation only occurs in a minority of people with fair skin; however, most people simply tan when they are exposed to sunlight. In fact, these represent two separate physiological processes (burning and tanning). The former condition, scientific sunburn as a result of the human sunburn cycle, is mostly due to a genetic polymorphism involving the expression of very low levels of melanin in human skin since it can be corrected by wearing a sunscreen containing black sesame melanin [50 mg/ml] in a zinc oxide cream base [7.5%] [18–20]. It is also correlated with a high risk for skin cancer. Nonetheless, there may be other genetic factors like differences in DNA repair enzyme activity which can

have an extremely high risk of contracting a terminal case of COVID-19.

contribute to this unusual trait in certain individuals, as well [21].

Simultaneously, a surprising recent genetic association study has revealed that a major genetic risk factor for severe COVID-19 in humans may actually be inherited from Neanderthals. Outside the continent of Africa (0.3%), modern humans have inherited significantly more genetic material from other hominid species including Neanderthals (approximately 2%) and Denisovans [22]. Europeans and South Asians appear to have the greatest complement of Vindija Neanderthal genes from Croatia and a gene cluster on chromosome 3 inherited from this species has been identified as a risk locus for respiratory failure after infection with SARS-CoV-2. Among certain South Asian populations, up to 50% can carry at least one copy of this risk haplotype and the highest carrier frequency occurs in Bangladesh where 63% of the population carries it. In the UK it has been reported that individuals of Bangladeshi origin have roughly a two times higher risk of dying from COVID-19

**12**

than people of other nationalities [23].

Interestingly, there are high levels of air pollution in the two regions of China and Northern Italy that were hardest hit by the virus suggesting that environmental conditions can have an impact on the infectiousness of the disease [24]. Italian researchers have recently proposed an association between higher mortality rates in Northern Italy and peaks of particulate matter concentrations in this region. The most polluted northern provinces of Italy were found to have more infection cases than the less polluted southern provinces and this correlated well with ambient particulate matter concentrations that often exceeded the legal limit in these areas. All data for this study was collected prior to the lockdown [25]. Surprisingly, further research by the same group demonstrated that SARS-CoV-2 RNA was present on outdoor airborne particulate matter that was collected from an industrial site in Bergamo, Italy. This evidence suggests that, under the right atmospheric conditions, SARS-CoV-2 could create clusters with particulate matter and enhance persistence of the virus in the atmosphere by facilitating its capacity for diffusion. However, the vitality and virulence of the coronavirus diffused via this method remain to be confirmed [26].

This could have been a significant factor in the spread of the coronavirus in highly polluted and populated cities like Mumbai, India. Social conditions such as crowding in slums have also been considered contributory to dispersal of the virus in developing countries like Brazil and India. Proximity to infected individuals increases the risk of person-to-person transmission since the SARS-CoV-2 virus is spread mainly by respiratory droplets, but can be aerosolized, too [3].

No matter how healthy an individual may be, the more exposure they have to a particular virus, the greater risk they have of contracting the disease. The greater the number of particles of the virus one is exposed to, the greater the chance that they will overwhelm the body and immune responses. This is the reason that young doctors and other frontline healthcare workers are getting serious cases of COVID-19 and dying at a higher frequency than the general population.

**View of Downtown Mumbai – December 2019**

**View of Mumbai Harbour – December 2019**
