Ahmad Ibsais
70 min readFeb 20, 2021

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COVID-19: A Biological Breakdown of SARS-CoV-2 and its Public Health Implications

Authors: Ahmad R. Ibsais, Emma J. Ziegenbein, Leyka Rumalla, Aine J. Booth, Asia Elbooz, Abhik Tallada

Abstract:

Coronavirus Disease 2019 emerged from severe acute respiratory syndrome coronavirus 2 is the latest global health emergency — launching a modern pandemic. The virus was first identified in Wuhan City, Hubei Province, China, as a respiratory illness. COVID-19 presents itself within 2–14 days after exposure to the virus, causing: fevers, chills, shortness of breath, difficulty breathing, and fatigue, which can be fatal to immunocompromised individuals. While infected individuals may be asymptomatic, the virus can spread through respiratory droplets inhaled by an individual in close distance. Across the world, over 150 nations are racing to produce candidate vaccines, bypassing FDA/international procedures, to release over two billion safe doses. Here, we cover an overview of the virology, epidemiology, origin of the virus, mode of transmission, vaccine development, and treatment, all while examining the disparities in COVID-19 related infection/treatment amongst racial minorities.

Introduction:

Initially reported to the World Health Organization (WHO) in late December 2019, the numerous unknown respiratory illnesses which spread across China (CDC, 2020) , became known as Coronavirus Disease 2019 (COVID-19), a form of SARS-CoV-2 (SARS-CoV-2). The virus quickly spread throughout Wuhan, China, with no indications of known pathology or transmission. Scientists in China had no treatments for those infected, experiencing heavy respiratory symptoms. The initial transmission of the virus is unknown, but it is thought to have originated from Huanan Seafood Market from an unknown animal source (Yuen et al., 2020). On March 11, 2020, WHO declared COVID-19 a global pandemic; as of August 31st, 2020 there are 25.3 million confirmed cases (John Hopkins University, 2020).

A study by the University of Hong Kong found a transmission rate of 83% within familial settings, indicating the high infection rate of COVID-19 (Yuen et al., 2020). This study also found that manifestations of the virus ranged from mild to severe, with more severe cases found in older patients. In most cases, COVID-19 presents less severely than SARS-CoV (Chan et al., 2020). Once declared a global pandemic, the response by countries varied, some enacting stricter regulations than others to contain the virus. The variation in government regulation resulted in major outbreaks across Europe, the Middle East, and eventually the United States. To save lives and slow the spread of the virus, major cities and nations enacted full lockdowns, stay-at-home orders, and executive orders to take preventative measures. These measures have put brakes on the global economy, but with no vaccine in sight and hospitals without resources, there seemed to be no other choice.

COVID-19 is a self-limiting disease in 80% of patients; however, with high infection rates and the global death toll rising each day, it is imperative to examine the molecular biology of SARS-CoV-2. Here, we examine COVID-19 against other strains of coronaviruses, the origin of this virus, methods of testing and treatment, epidemiology, and why the virus impacts communities of color at higher rates. We will also examine current developmental strides in vaccines, and future public health implications that have arisen as a result of the virus. As a disclaimer, this article is a review of extensive research conducted by wet-labs and leading epidemiologists.

History of Coronaviruses:

Coronaviruses (CoVs) are single stranded positive sense RNA (ssRNA+) viruses that typically cause respiratory illnesses in humans, with a number of other conditions in laboratory and domestic animals (Monto, 1976). The name Coronavirus was adopted after the characteristic crown-like projections seen on electron microscopy (Monto, 1976). These 20 to 40 nm club shaped projections give the virus crown-like features (Fehr & Perlman, 2015; Ksiazek et al., 2003; Pal et al., 2020). This distinguishing characteristic is reflected in their name, as the word “corona” translates to “crown” in Latin. Coronaviruses belong to the Nidovirales order, which is comprised of the Arteriviridae, Coronaviridae, Mesoniviridae, and Roniviridae families (Fehr & Perlman, 2015; Gorbalenya et al., 2006; Pal et al., 2020; Snijder et al., 2003; Sevajol, 2014). The Coronaviridae family is made up of the Coronavirinae and Torovirinae subfamilies, and is estimated to be responsible for up to 15% of common colds (Cui et al., 2018; Fehr, Perlman, 2015; Forni et al., 2017; Yang et al., 2020). The viruses found in the Coronavirinae subfamily range between 80 to 160 nm in diameter and 27 to 32 kb in genome length (Cui et al., 2018; Fehr, Perlman, 2015; Ye et al., 2020). The Coronovirinae subfamily is further divided into the alpha-coronavirus, beta-coronavirus, gamma-coronavirus, and delta-coronavirus genera (Cui et al., 2018; Fehr & Perlman, 2015; Wong et al., 2016). Of the four genera found in the Coronavirinae subfamily, the beta-CoV genus is mainly responsible for coronaviruses that infect humans, and can be further separated into 4 lineages: A,B,C, and D (Su et al., 2016; Wong et al., 2016; Ye et al., 2020) .

The first human coronaviruses were isolated in different techniques by the United States and Britain at around the same time (Monto, 1976). Bradburne, Bynoe and Tyrrell showed this isolation in 1960 when their specimen B814 had been passed serially three times in human tracheal culture and was still able to cause colds on inoculation, which indicated that it replicated (Bradburne et al., 1967). In 1962 Hamre and Procknow isolated five agents from kidney cell cultures collected from five medical students with common colds (Hamre & Procknow, 1966). These agents exhibited a type of cytopathic effect that had not been seen before (Monto, 1976). This isolate was called 229E and was cultivated on the human diploid cell line Wi-38 (Yang et al., 2020). Patients infected with HCoV-229E, or isolate 229E, experienced symptoms typical of the common cold: headaches, sore-throat, nasal discharge, sneezing, etc. Roughly 10 to 20% of those patients also developed a fever or cough (Su et al., 2016). Although HCoV-229E is relatively transmissible, it is not very virulent. Most patients infected with HCoV-229E experience mild cold-like symptoms, and typically only immunocompromised patients exhibit severe respiratory distress (Ye et al., 2020). HCoV-229E has a relatively short incubation period ranging from 2 to 5 days, and spreads through droplet transmission and fomites, which is any inanimate object that can transfer disease to a new host (Ye et al., 2020).

The 2003 Severe Acute Respiratory Syndrome (SARS-CoV) outbreak was due to a strain of coronavirus that was discovered in Hong Kong (Falsey & Walsh, 2003). A total of 8,096 cases of SARS-CoV were reported across 37 countries, and the virus was responsible for 774 deaths, yielding a case mortality rate of 9.6% (Cheng et al., 2007; Ye et al., 2020). In SARS-CoV patients, nearly 40% of patients developed respiratory failure that required ventilation (Falsey & Walsh, 2003). In terms of transmission, SARS-CoV can be spread through droplet, fomite, and fecal- oral modes of transmission (Ye et al., 2020). Since nearly 33% of preliminary cases of SARS-CoV were identified to be food handlers and people who were exposed to game animals, SARS-CoV was suspected to be of zoonotic origin. This was the first coronavirus pandemic with the ability to spread from person to person through droplets (Yang et al., 2020). In many SARS-CoV cases, the onset of symptoms was acute and sudden, with the initial symptoms usually being fever, chills and generalized myalgia (Yang et al., 2020). SARS-CoV is especially dangerous for immunocompromised patients as it can trigger severe immune responses, such as cytokine storms, which are potentially fatal for immunocompromised patients (Su et al., 2016; Ye et al., 2020). SARS-CoV impacted healthcare workers in Hong-Kong immensely due to nosocomial (hospital) infections (Tam et al., 2004). In a study done by researchers in 2004, questionnaires were sent to frontline healthcare workers in Hong Kong in order to identify psychological distress (Tam et al., 2004). This study found that 68% of healthcare workers reported a high level of stress, and 57% of workers were found to have experienced psychological distress (Tam et al., 2004). The frontline workers in Hong Kong were at a high risk of infection and of spreading disease to others and they worked under extreme stress and faced many losses and threats (Tam et al., 2004). “SARS stimulated healthcare workers to develop complex feelings towards their careers and perceptions of control” (Tam et al., 2004).
Middle East Respiratory Syndrome (MERS-CoV) was isolated from a patient in 2012 and subsequently caused 858 deaths and 2494 cases in 27 countries (Yang et al., 2020). As of February 2020, roughly 2,494 cases of MERS-CoV and 858 MERS-CoV related deaths have been confirmed across 27 countries, yielding a case mortality rate of 34.4% for the MERS-CoV (Su et al., 2016; Ye et al., 2020). The MERS-CoV outbreak in 2012 was mainly restricted to middle eastern countries but was also found in a few European countries and Tunisia (Ye et al., 2020). The second outbreak of MERS-CoV in 2015 was mainly limited to South Korea (Ye et al., 2020). The relatively high pathogenicity and mortality rate of MERS-CoV reduce the virus’s transmissibility, which helps explain why MERS-CoV outbreaks were much more regionally restricted than less pathogenic coronavirus outbreaks such as the SARS-CoV or SARS-CoV-2 outbreaks. In terms of transmission, MERS-CoV can be spread through droplet and fomite modes of transmission (Su et al., 2016; Ye et al., 2020). Although bat CoVs related to MERS-CoV have been found and bats were considered to be the reservoir host in the case of SARS-CoV, they are not considered to be so in the case of MERS-CoV. MERS-CoV has an incubation period of 5 to 14 days and the median time from onset of symptoms to hospitalization is 4 days (Zumla et al., 2015). For MERS-CoV the median time from onset of symptoms to death is 11.5 days (Zumla et al., 2015). Similar to SARS-CoV, around a third of MERS-CoV patients have gastrointestinal symptoms like vomiting and diarrhea (Zumla et al., 2015). In the most severe cases, MERS-CoV causes acute highly lethal pneumonia and renal dysfunction or failure is common in patients (Zumla et al., 2015). One of the distinguishing symptoms of MERS-CoV is acute renal failure: approximately 30% of all patients diagnosed with MERS-CoV exhibited gastrointestinal distress (Ye et al., 2020; Zumla et al., 2015). Another distinguishing characteristic of MERS-CoV is that roughly 75% of all reported cases had comorbidities, and those who died from MERS-CoV were more likely to have a comorbidity than not (Su et al., 2016; Zumla et al., 2015).

In addition to the aforementioned pathogenic HCoVs, less pathogenic community-acquired HCoVs have also been in circulation throughout human populations. To date, four major community-acquired HCoVs have been identified. The first two, HCoV-229E and HCoV-OC43, were identified in 1966 and 1967, respectively (Su et al., 2016). They are symptomatically indistinguishable, as infection with either virus typically results in cold-like symptoms: headaches, malaise, sore throat, etc. (Su et al., 2016). Although they both manifest in clinically identical manners, HCoV-229E and HCoV-OC43 are not directly related; HCoV-229E is an alpha-CoV whereas HCoV-OC43 is a Lineage A beta-CoV (Lau et al., 2011; Ye et al., 2020). These two community acquired HCoVs are thought to be responsible for 15% to 30% of all common respiratory tract infections (Lau et al., 2011). HCoV-OC43 and HCoV-229E occur globally, and case rates for these viruses typically spike in the winter seasons of temperate regions (Su et al., 2016; Ye et al., 2020).

The last two major community-acquired HCoVs to be discovered, HCoV-HKU1 and HCoV-NL63, were both first reported in 2004 in Hong Kong and the Netherlands, respectively (Forni et al., 2017; Su et al., 2016; Ye et al., 2020). Although HCoV-229E and HCoV-OC43 were symptomatically similar, HCoV-HKU1 and HCoV-NL63 are distinguishable by their symptoms. Symptoms associated with HCoV-HKU1 include fever, nasal discharge, dyspnea, bronchiolitis, and pneumonia (Su et al., 2016; Ye et al., 2020). Symptoms associated with HCoV-NL63 include croup, rhinorrhea, fever, conjunctivitis, bronchiolitis, etc (Su et al., 2016; Ye et al., 2020). Both HCoV-NL63 and HCoV-HKU1 are globally occurring viruses in the human population (Su et al., 2016).

Molecular Structure of SARS-CoV-2:

Figure#1A details virus entry

Figure#1B detailing S1 and S2 cellular processes

Couso, J., Patraquim, P. Classification and function of small open reading frames. Nat Rev Mol Cell Biol 18, 575–589 (2017). https://doi.org/10.1038/nrm.2017.58

The Coronavirus structure is crucial towards understanding its function and alarmingly rapid spread throughout the human population. Understanding the structure provides useful insight towards the COVID-19 compatibility with the human CD26 protein (CDC, 2019). The proteins surrounding the spherical virus proved to be pivotal towards understanding how COVID-19 interacts with humans. The surface of the virus is covered in glycoproteins or amino acid chains with carbohydrate groups attached to these chains. They are referred to as “ spike glycoprotein” due to the protruding nature of the spikes on the surface of the virus. These spikes attach to the host cell and fuse with the host’s membrane, enabling virus entry (Wrapp et al., 2020). The inside is immersed in single-stranded RNA and a HEMagglutinin-esterase protein which is a protein crucial for intracellular transport (Mousavizadeh et al., 2020). In comparison to other Viral structures, Coronaviruses contain the largest genomes (Mousavizadeh et. al., 2020.)

Each different, novel Coronavirus contains different ORF’s (abbreviated from Open Reading Frames). These are codons that contain start and stop, three-lettered codons. These ORF’s vary slightly between different conserved genes in Coronaviruses (ORF1ab, spike, envelope, membrane and nucleocapsid) (Mousavizadeh et. al., 2020.) Another differentiating factor is the slight alteration of the nucleocapsid proteins in different strains of Coronavirus (Mousavizadeh et. al., 2020.) In each membrane, the Coronavirus contains three to four viral proteins in the membrane with the most copious one being the (M) Glycoprotein (Mousavizadeh et. al., 2020.)The Glycoprotein leaves the NH2 Terminus on the outside of the virus which is an indicator of the beginning of a polypeptide signified by the free NH2 group. The glycoprotein then ends on the inside of the virus at the elongated COOH terminus which is an indicator of the end of the polypeptide chain (Mousavizadeh et. al., 2020.)

Figure #2 shows the evolution of Open Reading Frames (ORF’s and demonstrates the start and stop codon Couso, J., Patraquim, P. Classification and function of small open reading frames. Nat Rev Mol Cell Biol 18, 575–589 (2017). https://doi.org/10.1038/nrm.2017.58

Along with the (M) Glycoprotein is the (S) Spike Protein on the surface of the virus. This is the protein that constitutes the Spike Glycoprotein that the Coronavirus is infamously known for in its protruding spikes encasing the surface of the molecule. The (S) Spike Protein’s primary function is to neutralize Antibodies acting as a defense mechanism on the surface of the virus (Mousavizadeh et. al., 2020.) The (M) Glycoprotein is responsible for synthesizing virus particles inside of the virus independent of the Spike Protein (Mousavizadeh et. al., 2020.)

The spike glycoproteins are the primary source of adhesion to human cells and they assist in membrane fusion. On each surface are two subunits, S1 and S2. These two respective subunits mediate the fusion of membranes through different pathways, each occurring separately and consecutively (Wrapp et al., 2020.) Proteins on the surface known as nucleocapsid proteins are crucial to the function of the virus in itself for replicating and for mediating transfusion (Gutsche et al., 2015.) The Nucleocapsid proteins are crucial and practically a necessity towards the functioning of the virus enabling many of its daily functions such as RNA synthesis. These proteins contain the N and C terminals crucial to S1 (Wrapp et al., 2020.) The N Terminal is the RNA- binding site or NTD while the C-terminal is the dimerization domain. These are critical for oligomerization and RNA binding in a host cell.

Each spike is a trimeric protein or in this case, three proteins that are not chemically bonded to one another. The spike glycoproteins are the primary source of adhesion to human cells and assists in membrane fusion. On each surface are two subunits, S1 and S2 (Wrapp et al., 2020). These two respective subunits mediate the fusion of membranes through different pathways. There are proteins on the surface known as nucleocapsid proteins and these are crucial to the function of the virus in itself for replicating and for mediating transfusion. These proteins contain the N and C terminals crucial to S1. The N Terminal is the RNA- binding site or NTD while the C-terminal is the dimerization domain (Wrapp et al., 2020). Either NTD or the C-Terminal can serve the purpose of a place for membrane fusion and binding depending on the host cell it wants to bind to. This varies within molecules but COVID-19 primarily uses the N-domain to bind to other receptors on a host cell as do other forms of CoV’s including SARS-CoV and MERS-CoV.

When the trimeric protein structure fuses with the host membrane, its structure changes drastically (Wrapp et al., 2020). When the S1 subunit attaches to the host cell, the trimer protein discussed above becomes unstable. The destabilization of this trimer eliminates the S1 subunit and proceeds to move into the S2 subunit (Wrapp et al., 2020). This results in the trimer stabilizing again to another conformation after fusing with the host cell’s membrane. This conformation conceals the receptor binding sites and enables fusion with a host cell. The structure of the Coronavirus contains ridges that allow much more efficient and effective fusion with the membrane of its host cell which is why it is so effective in fusion with the Human Cells, its rapid spread and compatibility make it a detrimental force. The effectiveness of the Coronavirus in spreading among people is due primarily to ridges on its surface and the spike-like proteins amassed on its surface. Understanding the SARS-CoV 2019 structure enables a better understanding of possible treatment.

Treatments have been targeting the primary protease in the molecule (protein disassembling enzyme) referred to as the Mpro (Zhang et al., 2020). This enzyme is imperative towards the processing of larger polyproteins synthesized by the RNA in the virus. On the virus, there remains to be nothing less of eleven individual targeted sites on the molecule for Mpro cleavage (Zhang et al., 2020). Inhibiting the Mpro enzyme is the answer towards putting viral replication to a halt indicating how crucial this enzyme is inhibiting replication (Zhang et al., 2020). The peptidomimetic α-ketoamides was synthesized as broad-spectrum inhibitors by scientists to inhibit these primary proteases (Zhang et al., 2020.).

Epidemiology of SARS-CoV-2: (combined w/ Mechanism of infection)

The natural host of SARS-CoV-2 are bats and humans are the terminal host (Wang et al., 2020). The intermediate host of the virus are Pangolins, and they act as a reservoir for sexually immature parasites while they mature (Wang, et al., 2020). The source of infection is from other COVID-19 patients and severe patients are considered more contagious than mild cases (Jin et al., 2020). The basic reproductive values or basic reproductive ratio of infectious agents is a metric used to describe the contagiousness or transmissibility. Basic reproductive values or R0 (pronounced R naught) is almost always measured retrospectively using seroepidemiological data or theoretical mathematical models. The basic reproductive values (R0 ) of COVID-19 is two to three and a half, which means that an infected person could spread the disease to two or three people (Wang et al., 2020). The entry mechanism of COVID-19 varies depending on cellular proteases, some of which include, human airway trypsin-like protease (HAT), cathepsins and transmembrane protease serine 2 (TMPRSS2) that split the spike protein and establish further penetration changes (Cowling & Aiello, 2020). COVID-19 is placed in Category B of infectious agents. Therefore, it is described as moderately easy to disseminate, resulting in moderate morbidity rates and low mortality rates. However, it still requires the CDC’s observation (Singhal, 2020). The China National Health Commission recommends that COVID-19 be treated as a Category A infectious agent, meaning it should be considered high priority.

SARS-CoV-2 is considered a self-limiting disease and most mild cases can recover in one to two weeks (Jin et al., 2020). Symptoms often appear after the incubation period, which is around 5.2 days, but has an estimated upper limit of 14 days (Cowling & Aiello, 2020 ; Rothan & Byrareddy, 2020). COVID-19 spreads from human to human via respiratory droplets, explaining why large gatherings of people in close proximity can lead to an increased number of people contracting the virus. COVID-19 can also be transmitted before symptoms begin and from asymptomatic people, which aids in the rapid spread of the virus between humans. Infection of COVID-19 begins as a mild upper respiratory injury and can progress into a severe respiratory disease (Shereen et al., 2020). The most common symptoms are fever, fatigue, myalgia, and cough followed by sputum production, headaches, and diarrhea (Jin et al., 2020). Smoking, drinking, asthma, diabetes, cardiovascular disease, and cancer can increase susceptibility to the disease and are considered comorbidity factors (Jin et al., 2020). Elderly individuals and those with underlying comorbidities are especially vulnerable to the virus. 50 to 75 percent of cases in the elderly and individuals with underlying comorbidities were fatal, according to data from January to March 2020. However, fatality in hospitalized patients ranges from 4 to 11 percent, while the overall fatality rate is estimated to range between 2 and 3 percent (Singhal, 2020). COVID-19 shows unique clinical symptoms that target the gastrointestinal system like diarrhea. It should be noted that a low number of SARS and MERS patients had gastrointestinal issues (Rothan & Byrareddy, 2020). The virus can also progress to pneumonia, respiratory failure, and even death. While the virus has an upper incubation period of 14 days, the median time for onset of symptoms is five days, hospitalization for 7–10 days, and recovery following the second or third week of infection (Singhal, 2020). There are five categories that SARS-CoV-2 infections can fall into: asymptomatic, mild to medium, severe, critical and death (Jin et al., 2020). Nosocomial infection is a major issue with COVID-19, with many treatments for COVID-19 being high-risk factors for nosocomial transmission like intubation, bronchoscopy examination, patient transport and manual ventilation (Wang et al., 2020). To prevent the spread of the virus, face masks or face coverings are suggested (Cheng et. al, 2020). However, the efficacy of face masks protecting healthy individuals from the virus is unclear. Nevertheless, face masks are promoted because they may protect others from one’s own germs which is especially important because the virus can spread from an asymptomatic individual. A combination of face masks and proper hand hygiene has shown to reduce the transmission of the virus in communities (Cowling & Aiello, 2020).

The initial outbreak of COVID-19 was in Wuhan, China and the surrounding cities on December 8th, 2019. The first reported case in another province was on January 19th, 2020 in Guangdong. (Jin et al., 2020). By January 30, the first case in Tibet Province was reported and COVID-19 had spread to all of mainland China (Jin et al., 2020).

COVID-19 Testing:

There are the two distinct types of COVID tests, but a more detailed look shows that there are four subcategories of tests that people depend on to get a diagnosis and for further regulation. These four tests are serological tests, nucleic acid, antigen, and ancillary tests (Weissleder, et al., 2020). They each play a critical role in diagnosing COVID to the spectrum of people seeking to be tested, whether it be by detection or by tests done once a patient has been diagnosed with COVD. Before these tests can be understood, a basic comprehension of how detection is possible is crucial towards understanding how treatment relates to the structure of the virus and the human body.

For Nucleic Acid Tests, RNA is reverse-transcribed or made into DNA. This DNA is then amplified using the Polymerase Chain Reaction, which is a way to replicate the DNA strand into billions of copies of itself. This rapid replication also allows for amplification of the gene being targeted and replicated. The regions replicated vary depending on the virus. The U.S. Food and Drug Administration (FDA) and Centers for Disease Control and Prevention (CDC) decided on choosing the viral nucleocapsid N1, N2, and human RNase P gene to replicate and amplify versus how the World Health Organization recommended that individuals target and replicate the CoV-2 RNA-dependent RNA polymerase (RdRP) and envelope (E) genes (Weissleder et al., 2020). Different gene markers hold varied sensitivities towards the virus and can be crucial in its detection (Weissleder et al., 2020). These, in particular, are all markers that enable SARS-CoV-2 detection due to the acute sensitivity these replicated genes have for the virus.

Figure 1 shows Reverse Transcription Reverse Transcription Applications: Thermo Fisher Scientific — US. (n.d.). Retrieved from https://www.thermofisher.com/us/en/home/life-science/cloning/cloning-learning-center/invitrogen-school-of-molecular-biology/rt-education/reverse-transcription-applications.html

Serological tests, better known as Antibody Tests, depend on the specificity of ligands to bond to components of the host’s immune system, such as their immunoglobulin, which are commonly known as antibodies, and interleukin, and evaluate these particular proteins (Weissleder, et al., 2020.) These ligands are called “affinity ligands”, or ligands that bond with a specific antibody with a very high affinity towards the antibody. This comes with keen accuracy and specificity towards the antibody being targeted. The specificity of these ligands ensure that the information obtained is strictly for past and present exposure to SARS-CoV-2. The specificity of serological tests go so far as to differentiate infections caused by SARS-CoV-2 from other novel Human Coronaviruses. Serological testing helps determine past exposure to SARS-CoV-2, immunity in order to aid with vaccine development, and current exposure.

Antigen Tests, or Viral Tests, contain a high specificity towards a certain virus and the protein markers on a virus are indicators of its identity (Weissleder, et al., 2020). Antigen Tests only show current infection and not previous exposure unlike the Antibody Test. For SARS-CoV-2, the Nucleocapsid proteins and spike proteins on the surface of the virus are used to detect current exposure using ELISA or enzyme-linked immunosorbent assay (Weissleder, et al., 2020). The ELISA test identifies IgG and IgM antibodies in the host (Macdonald, et. al., 2020). Antibodies are created in response to a particular antigen so the detection of these antibodies can determine whether or not COVID is present. This test is done by using a nasopharyngeal swab, a medical professional inserts a cotton swab up the individual’s nose and moves the cotton swab around for about fifteen seconds (CDC, 2020).

Ancillary Tests are used for COVID patients and management of their vitals or condition. This includes various laboratory tests such as checking for cytokine storms and performing blood coagulation tests. These tests serve as regulators in order to ensure that a COVID patient is stabilized.

Drug Development:

Currently, there is no available vaccine for COVID-19. However, there is a vast number of researchers working to develop a variety of vaccines as well as restorative strategies to survive the virus. Research finds that several drugs have in vitro activity against the virus, but there is no clinical evidence that supports the efficacy and safety of any vaccines specifically against COVID-19 in humans (Kalil, 2020). However, genomic sequence information, in addition to protein structure modeling, has allowed scientists to develop a list of existing vaccinations that might have restorative potential for COVID-19.

When creating an antiviral vaccine, there are multiple categories including inactive or live-attenuated viruses, virus-like particles (VLP), viral vectors, protein-based, DNA-based, and mRNA-based vaccines. Vaccinations including a live-attenuated virus, viral vectors, inactivated virus, subunit vaccines, recombinant DNA, and proteins vaccines are being tested on animals (Li et al., 2020). Currently, a mRNA-based vaccine prepared by the US National Institute of Allergy and Infectious Diseases against COVID-19 is under phase 1 trial (Shereen et. al., 2020). However, a major concern while testing vaccines is whether or not it is ethical to give patients a placebo. It must be noted that it is not possible to accurately determine the harms of an experimental drug or vaccine without a control group (Kalil, 2020).

Due to new drug development being a long process, vaccines for other diseases are being examined for cross-resistance for COVID-19. The idea of cross-resistance was observed in China when children being vaccinated for the measles were less vulnerable to the virus (Shereen et al., 2020). However, scientists are working on long-term drug development goals for the virus that include identification of inhibitors aimed at the replication or infection processes associated with the virus (Liu et al., 2020).

Non-Vaccinal Methods of Treatment for COVID-19:

Although a vaccine is the best long-term solution for dealing with SARS-CoV-2, there are many other forms of treatment currently available. These forms of treatments can be split into two approaches: disrupting the CoV replication cycle and regulating the human immune response (Tu et al., 2020). The three main ways non-vaccinal drugs disrupt the CoV replication cycle are through interfering with genomic CoV ssRNA chain synthesis, interfering with viral proteases, and preventing viral cell entry (Li et al., 2020; Pruijssers et al., 2019; Tu et al., 2020). In terms of regulating immune response, non-vaccinal drugs have been used both to elevate and to attenuate immune responses, depending on the case (Li et al., 2020; Tu et al., 2020). For example, immunocompromised patients suffer from an excessive immune response, which can cause significant internal damage. In order to mitigate the amount of damage COVID-19 causes in these patients, immunosuppressive drugs are employed to prevent the immune system from overreacting. In the case of a patient with a weakened immune system, medical therapies and treatments are available to boost the immune response.

Disrupting CoV Replication Cycle: Interfering with Genomic CoV ssRNA Chain Synthesis

The most promising drug that disrupts genomic CoV ssRNA chain synthesis is Remdesivir (Tu et al., 2020). Remdesivir, a prodrug analogue of the adenosine nucleoside, is a type of nucleoside analogue inhibitor that interferes with CoV ssRNA chain synthesis (Li et al., 2020). Nucleoside (and nucleotide) inhibitors (NIs) are man-made analogues of their parent nucleoside/nucleotides but with their sugar molecule or heterocyclic ring altered so that the NI is dysfunctional or incompatible with the viral RNA-dependent RNA Polymerases (RdRp) (Pruijsssers et al., 2019). NIs interfere with CoV ssRNA chain synthesis through three main mechanisms.

One way they interfere is through introducing harmful mutations; since NIs are nucleosides that are modified to be dysfunctional, they mispair with other nucleosides during chain elongation, introducing harmful mutations as they incorporate into the new viral genome (Pruijsssers et al., 2019). NIs also interfere with CoV ssRNA chain synthesis by triggering premature chain termination; the incorporation of foreign nucleotides, such as NIs, into nascent viral RNA can cause the RdRp machinery to malfunction and prematurely terminate chain growth (Pruijsssers et al., 2019). Another way NIs interfere with CoV ssRNA chain synthesis is through competing with the natural population of nucleosides to decrease cellular nucleoside levels (Pruijsssers et al., 2019). This in turn leads to less available “healthy” nucleosides in the cell, which also results in premature chain termination as there are not enough nucleosides to elongate the viral ssRNA chain. Remdesivir exhibits broad spectrum antiviral activity against many types of viruses and holds significant potential in the treatment of COVID-19 (Guo et al., 2020; Li et al., 2020; Tu et al., 2020). Drug development against SARS-CoV-2 has proven difficult because of CoVs unique proofreading capabilities (Pruijsssers et al., 2019). Part of the CoV genome encodes for nonstructural protein 14 (nsp14), which serves as an exoribonuclease with 3’ to 5’ proofreading activity (Pruijsssers et al., 2019). Despite the CoV’s proofreading mechanism, Remdesivir has been shown to yield clinically positive results. Remdesivir was administered to the first patient in the U.S. reported to have COVID-19 on the 7th day of infection, and the patient’s condition improved by the 8th day (Guo et al., 2020).

Disrupting CoV Replication Cycle: Interfering with Viral Protease

Viral proteases are enzymes that are encoded for by the viral genome to cleave other viral proteins into their appropriate lengths and sizes. Interfering with or inhibiting viral protease function can decrease the overall viral expression and load in the host (Tu et al., 2020). For example, the HIV genome encodes for aspartyl protease, the enzyme responsible for cleaving the necessary proteins to create a new HIV virion (Tu et al., 2020). In order to treat AIDS, aspartyl protease inhibitors, such as lopinavir and ritonavir, are employed to decrease the viral expression and load of HIV in the host (Guo et al., 2020; Tu et al., 2020). Although the CoV genome encodes for a cysteine protease rather than an aspartyl protease, it is hypothesized that lopinavir and ritonavir can also inhibit the 3CL1 protease function in CoVs (Tu et al., 2020). Clinical studies have yielded mixed results on the efficacy of lopinavir and ritonavir in the treatment of COVID-19: some have shown that lopinavir and ritonavir improved the patient’s condition while others show no clinical benefit (Tu et al., 2020). More clinical studies are under way to determine the efficacy of lopinavir and ritonavir (Pruijsssers et al., 2019).

Disrupting CoV Replication Cycle: Preventing Viral Cell Entry

Hydroxychloroquine is one of the most promising drugs that prevents viral entry of SARS-CoV-2 into the host cell (Tu et al., 2020). Hydroxychloroquine increases the endosomal pH, making it difficult for SARS-CoV-2 virions to enter the host cell (Li et al., 2020; Tu et al., 2020). Hydroxychloroquine has shown to reduce viral load and expression of SARS-CoV-2 in in vitro testing as well, which shows promise for future clinical trials (Tu et al., 2020). However, it should be noted that, so far, clinical studies have yielded mixed results for the efficacy of hydroxychloroquine. (Tu et al., 2020)

Regulating Immune Response: Elevating the Immune Response

There are two main ways to enhance the immune response; addition of natural killer (NK) cells, and interferon therapy (Tu et al., 2020). NK cells are a class of cytotoxic T cells that play a central role in the immune response. They identify and respond to specific antigens, killing virus-infected cells before they can infect other healthy cells. NK cell therapy is currently under phase I trial in China, but researchers predict that NK cell therapy has significant potential in decreasing viral load and expression of SARS-CoV-2 (Tu et al., 2020). Interferons are a type of cytokines, or immunological agents, secreted by virus-infected cells that alert surrounding cells to heighten their antiviral defenses. Interferon therapy has shown broad spectrum antiviral activity and is predicted to decrease viral load and expression in SARS-CoV-2 (Tu et al., 2020). Clinical trials are currently underway to develop a safe and efficient interferon therapy for COVID-19 (Tu et al., 2020).

Regulating Immune Response: Attenuating the Immune Response

Intravenous Immunoglobulin (IVIG) regulates the immune system in a dose dependent manner (Tu et al., 2020). In low doses (0.2–0.4 g IVIG / kg body weight), it can be used to help treat antibody deficiencies, but in higher doses (2 g IVIG / kg body weight), IVIG displays immunosuppressive activity, as it prevents inflammatory cell growth and phagocytosis (Tu et al., 2020). IVIG has been commonly used in the fields of dermatology and neurology, and is currently undergoing clinical trials for treatment with COVID-19 (Tu et al., 2020). It shows significant promise for immunocompromised patients who suffer from exacerbated immune responses.

Public Health: Effects on Racial Minorities and Underprivileged Populations:

It is considered common knowledge that racial and ethnic minority populations face higher rates of health risks. These risks come about due to health disparities between racial and ethnic groups regarding health insurance coverage, quality of care, and access to care. For example, according to the United States Census Bureau’s report on Health Insurance Coverage in 2017, non-hispanic Whites had the lowest uninsured rate (6.3 percent), while Hispanics had the highest uninsured rate (16.1 percent) among other racial and ethnic groups (U.S. Census Bureau, 2018).

Health outcomes and disparities between racial groups are inevitably attributed to income. Lower incomes can indicate less access to medical resources and care. According to the U.S. Census Bureau, Blacks and Hispanics have had the lowest median household incomes since 1967 (U.S. Census Bureau, 2018). Therefore, racial minority status and socioeconomic status are interrelated.

Figure 1. Graph showing median household incomes for different racial groups from 1967 to 2018. Retrieved from: U.S Census Bureau, Current Population Survey, 1968 to 2019 Annual Social and Economic Supplements.

It is extremely important to understand that socioeconomic status is a significant social determinant of health. For more information on how poverty impacts health outcomes, visit this page by the Office of Disease Prevention and Health Promotion: Poverty.

The global COVID-19 pandemic has made health inequities in the United States very evident (Dorn et al., 2020). In fact, African Americans and other racial minorities have been disproportionately affected by the pandemic. Deaths due to COVID-19 are disproportionately higher for African American communities. For example, according to data from January to April 2020, all but three people who died as a result of COVID-19 in St. Louis, Missouri were African American (Dorn et al., 2020). According to the official website of the city of St. Louis, African Americans now have a death rate of 84.2 percent, while Caucasians have a death rate of 42.4 percent (St. Louis City Government). In a preliminary study conducted by the CDC, compiled data from hospitals in 14 states found that 33 percent of COVID-19 hospitalizations were African American individuals, despite representing only 18 percent of the total population studied (Garg et al., 2020). In another study, death rates from COVID-19 in New York City were substantially higher for African and Latin Americans than that of Caucasians or Asian Americans (Kirby, 2020).

This evidence is not exactly surprising, as communities of color face higher rates of diseases than other communities. In fact, chronic conditions such as asthma, hypertension, kidney disease, and obesity, are more common in African American populations (Kirby, 2020). Native American populations also have higher levels of underlying health conditions, such as heart disease (Dorn et al., 2020). Cardiovascular health issues, especially those caused by viral infections such as myocarditis, lead to increased complications and risk of death due to COVID-19 (Masic et al., 2020).

Not only are communities of color disproportionately affected due to their underlying health conditions, but also due to their increased risk of exposure. According to the Economic Policy Institute, minority populations, and especially people of color, make up the majority of “essential workers” like janitors, grocery workers, and cashiers (McNicholas & Poydock, 2020). They especially make up the majority of essential workers in food and agriculture (McNicholas & Poydock, 2020). Additionally, people of color makeup 53 percent of essential workers in industrial, commercial, and residential facilities/services (McNicholas & Poydock, 2020). Unfortunately, these essential workers do not have the privilege to work remotely or from home. Also, oftentimes, working in these industries signifies a lack of health insurance, which exposes the systemic inequalities in the United States (Dorn et al., 2020). As stated by the CDC, these communities have an increased risk to contract COVID-19 due to the increased likeliness to live in more densely populated areas and housing, to use public transport more, and to work in lower service jobs without sick pay (Kirby, 2020). These communities lack “facilities to safely isolate or quarantine” (Kirby, 2020). This evidence is not only exclusive to the United States. In fact, the issue extends globally. In China, vulnerable and underprivileged populations were also disproportionately affected by COVID-19 when cases were high in January and February of 2020 (Wang & Tang, 2020).

Additionally, health promotion plays an extremely important role in public responses to the COVID-19 pandemic (Smith & Judd, 2020). Due to the digital age, health education is largely delivered through information technology and mass media. Unfortunately, the digital age negatively affects underprivileged communities more than others, which occurs due to a multi-faceted problem. E-readiness, or one’s ability to process digital/electronic information, is an extremely important sociological concept that affects how people respond to the COVID-19 pandemic. The relationship between e-readiness and public response to the pandemic is an extremely complex problem, because various factors such as age, education, and location (urban, suburban, and rural areas) can affect an individual’s e-readiness. Research shows that information technology, especially social media, leaves out those who lack access to it and those who do not use it frequently for a variety of reasons (Smith & Judd, 2020). Informative posts and messages about the pandemic, including preventative measures such as wearing masks and washing hands for at least 20 seconds, are published and promoted through information technology and the internet. This means that those with higher e-readiness can better understand these messages and are therefore more likely to take better preventative measures. Additionally, minority communities may have access to social media, but lack proper literacy skills to understand informative posts about the pandemic. Non-native English speakers also face language barriers and difficulties with translation after they have contracted COVID-19 and are hospitalized, causing increased anxiety and stress among these populations during treatment (Abuelgasim et. al., 2020). For more information on the digital divide and its effects on minorities (as well as minority child development), read these research papers: Closing the Digital Divide and its Impact on Minorities & Digital Inequality and Developmental Trajectories of Low-income, Immigrant, and Minority Children.

The COVID-19 pandemic has also disproportionately impacted minority unemployment. After state governments began implementing social distancing measures, the overall unemployment rate jumped to 14.7 percent (Fairlie et al., 2020).

COVID-19: A Biological Breakdown of SARS-CoV-2 and its Public Health Implications

Authors: Ahmad R. Ibsais, Emma J. Ziegenbein, Leyka Rumalla, Aine J. Booth, Asia Elbooz, Abhik Tallada

Abstract:

Coronavirus Disease 2019 emerged from severe acute respiratory syndrome coronavirus 2 is the latest global health emergency — launching a modern pandemic. The virus was first identified in Wuhan City, Hubei Province, China, as a respiratory illness. COVID-19 presents itself within 2–14 days after exposure to the virus, causing: fevers, chills, shortness of breath, difficulty breathing, and fatigue, which can be fatal to immunocompromised individuals. While infected individuals may be asymptomatic, the virus can spread through respiratory droplets inhaled by an individual in close distance. Across the world, over 150 nations are racing to produce candidate vaccines, bypassing FDA/international procedures, to release over two billion safe doses. Here, we cover an overview of the virology, epidemiology, origin of the virus, mode of transmission, vaccine development, and treatment, all while examining the disparities in COVID-19 related infection/treatment amongst racial minorities.

Introduction:

Initially reported to the World Health Organization (WHO) in late December 2019, the numerous unknown respiratory illnesses which spread across China (CDC, 2020) , became known as Coronavirus Disease 2019 (COVID-19), a form of SARS-CoV-2 (SARS-CoV-2). The virus quickly spread throughout Wuhan, China, with no indications of known pathology or transmission. Scientists in China had no treatments for those infected, experiencing heavy respiratory symptoms. The initial transmission of the virus is unknown, but it is thought to have originated from Huanan Seafood Market from an unknown animal source (Yuen et al., 2020). On March 11, 2020, WHO declared COVID-19 a global pandemic; as of August 31st, 2020 there are 25.3 million confirmed cases (John Hopkins University, 2020).

A study by the University of Hong Kong found a transmission rate of 83% within familial settings, indicating the high infection rate of COVID-19 (Yuen et al., 2020). This study also found that manifestations of the virus ranged from mild to severe, with more severe cases found in older patients. In most cases, COVID-19 presents less severely than SARS-CoV (Chan et al., 2020). Once declared a global pandemic, the response by countries varied, some enacting stricter regulations than others to contain the virus. The variation in government regulation resulted in major outbreaks across Europe, the Middle East, and eventually the United States. To save lives and slow the spread of the virus, major cities and nations enacted full lockdowns, stay-at-home orders, and executive orders to take preventative measures. These measures have put brakes on the global economy, but with no vaccine in sight and hospitals without resources, there seemed to be no other choice.

COVID-19 is a self-limiting disease in 80% of patients; however, with high infection rates and the global death toll rising each day, it is imperative to examine the molecular biology of SARS-CoV-2. Here, we examine COVID-19 against other strains of coronaviruses, the origin of this virus, methods of testing and treatment, epidemiology, and why the virus impacts communities of color at higher rates. We will also examine current developmental strides in vaccines, and future public health implications that have arisen as a result of the virus. As a disclaimer, this article is a review of extensive research conducted by wet-labs and leading epidemiologists.

History of Coronaviruses:

Coronaviruses (CoVs) are single stranded positive sense RNA (ssRNA+) viruses that typically cause respiratory illnesses in humans, with a number of other conditions in laboratory and domestic animals (Monto, 1976). The name Coronavirus was adopted after the characteristic crown-like projections seen on electron microscopy (Monto, 1976). These 20 to 40 nm club shaped projections give the virus crown-like features (Fehr & Perlman, 2015; Ksiazek et al., 2003; Pal et al., 2020). This distinguishing characteristic is reflected in their name, as the word “corona” translates to “crown” in Latin. Coronaviruses belong to the Nidovirales order, which is comprised of the Arteriviridae, Coronaviridae, Mesoniviridae, and Roniviridae families (Fehr & Perlman, 2015; Gorbalenya et al., 2006; Pal et al., 2020; Snijder et al., 2003; Sevajol, 2014). The Coronaviridae family is made up of the Coronavirinae and Torovirinae subfamilies, and is estimated to be responsible for up to 15% of common colds (Cui et al., 2018; Fehr, Perlman, 2015; Forni et al., 2017; Yang et al., 2020). The viruses found in the Coronavirinae subfamily range between 80 to 160 nm in diameter and 27 to 32 kb in genome length (Cui et al., 2018; Fehr, Perlman, 2015; Ye et al., 2020). The Coronovirinae subfamily is further divided into the alpha-coronavirus, beta-coronavirus, gamma-coronavirus, and delta-coronavirus genera (Cui et al., 2018; Fehr & Perlman, 2015; Wong et al., 2016). Of the four genera found in the Coronavirinae subfamily, the beta-CoV genus is mainly responsible for coronaviruses that infect humans, and can be further separated into 4 lineages: A,B,C, and D (Su et al., 2016; Wong et al., 2016; Ye et al., 2020) .

The first human coronaviruses were isolated in different techniques by the United States and Britain at around the same time (Monto, 1976). Bradburne, Bynoe and Tyrrell showed this isolation in 1960 when their specimen B814 had been passed serially three times in human tracheal culture and was still able to cause colds on inoculation, which indicated that it replicated (Bradburne et al., 1967). In 1962 Hamre and Procknow isolated five agents from kidney cell cultures collected from five medical students with common colds (Hamre & Procknow, 1966). These agents exhibited a type of cytopathic effect that had not been seen before (Monto, 1976). This isolate was called 229E and was cultivated on the human diploid cell line Wi-38 (Yang et al., 2020). Patients infected with HCoV-229E, or isolate 229E, experienced symptoms typical of the common cold: headaches, sore-throat, nasal discharge, sneezing, etc. Roughly 10 to 20% of those patients also developed a fever or cough (Su et al., 2016). Although HCoV-229E is relatively transmissible, it is not very virulent. Most patients infected with HCoV-229E experience mild cold-like symptoms, and typically only immunocompromised patients exhibit severe respiratory distress (Ye et al., 2020). HCoV-229E has a relatively short incubation period ranging from 2 to 5 days, and spreads through droplet transmission and fomites, which is any inanimate object that can transfer disease to a new host (Ye et al., 2020).

The 2003 Severe Acute Respiratory Syndrome (SARS-CoV) outbreak was due to a strain of coronavirus that was discovered in Hong Kong (Falsey & Walsh, 2003). A total of 8,096 cases of SARS-CoV were reported across 37 countries, and the virus was responsible for 774 deaths, yielding a case mortality rate of 9.6% (Cheng et al., 2007; Ye et al., 2020). In SARS-CoV patients, nearly 40% of patients developed respiratory failure that required ventilation (Falsey & Walsh, 2003). In terms of transmission, SARS-CoV can be spread through droplet, fomite, and fecal- oral modes of transmission (Ye et al., 2020). Since nearly 33% of preliminary cases of SARS-CoV were identified to be food handlers and people who were exposed to game animals, SARS-CoV was suspected to be of zoonotic origin. This was the first coronavirus pandemic with the ability to spread from person to person through droplets (Yang et al., 2020). In many SARS-CoV cases, the onset of symptoms was acute and sudden, with the initial symptoms usually being fever, chills and generalized myalgia (Yang et al., 2020). SARS-CoV is especially dangerous for immunocompromised patients as it can trigger severe immune responses, such as cytokine storms, which are potentially fatal for immunocompromised patients (Su et al., 2016; Ye et al., 2020). SARS-CoV impacted healthcare workers in Hong-Kong immensely due to nosocomial (hospital) infections (Tam et al., 2004). In a study done by researchers in 2004, questionnaires were sent to frontline healthcare workers in Hong Kong in order to identify psychological distress (Tam et al., 2004). This study found that 68% of healthcare workers reported a high level of stress, and 57% of workers were found to have experienced psychological distress (Tam et al., 2004). The frontline workers in Hong Kong were at a high risk of infection and of spreading disease to others and they worked under extreme stress and faced many losses and threats (Tam et al., 2004). “SARS stimulated healthcare workers to develop complex feelings towards their careers and perceptions of control” (Tam et al., 2004).
Middle East Respiratory Syndrome (MERS-CoV) was isolated from a patient in 2012 and subsequently caused 858 deaths and 2494 cases in 27 countries (Yang et al., 2020). As of February 2020, roughly 2,494 cases of MERS-CoV and 858 MERS-CoV related deaths have been confirmed across 27 countries, yielding a case mortality rate of 34.4% for the MERS-CoV (Su et al., 2016; Ye et al., 2020). The MERS-CoV outbreak in 2012 was mainly restricted to middle eastern countries but was also found in a few European countries and Tunisia (Ye et al., 2020). The second outbreak of MERS-CoV in 2015 was mainly limited to South Korea (Ye et al., 2020). The relatively high pathogenicity and mortality rate of MERS-CoV reduce the virus’s transmissibility, which helps explain why MERS-CoV outbreaks were much more regionally restricted than less pathogenic coronavirus outbreaks such as the SARS-CoV or SARS-CoV-2 outbreaks. In terms of transmission, MERS-CoV can be spread through droplet and fomite modes of transmission (Su et al., 2016; Ye et al., 2020). Although bat CoVs related to MERS-CoV have been found and bats were considered to be the reservoir host in the case of SARS-CoV, they are not considered to be so in the case of MERS-CoV. MERS-CoV has an incubation period of 5 to 14 days and the median time from onset of symptoms to hospitalization is 4 days (Zumla et al., 2015). For MERS-CoV the median time from onset of symptoms to death is 11.5 days (Zumla et al., 2015). Similar to SARS-CoV, around a third of MERS-CoV patients have gastrointestinal symptoms like vomiting and diarrhea (Zumla et al., 2015). In the most severe cases, MERS-CoV causes acute highly lethal pneumonia and renal dysfunction or failure is common in patients (Zumla et al., 2015). One of the distinguishing symptoms of MERS-CoV is acute renal failure: approximately 30% of all patients diagnosed with MERS-CoV exhibited gastrointestinal distress (Ye et al., 2020; Zumla et al., 2015). Another distinguishing characteristic of MERS-CoV is that roughly 75% of all reported cases had comorbidities, and those who died from MERS-CoV were more likely to have a comorbidity than not (Su et al., 2016; Zumla et al., 2015).

In addition to the aforementioned pathogenic HCoVs, less pathogenic community-acquired HCoVs have also been in circulation throughout human populations. To date, four major community-acquired HCoVs have been identified. The first two, HCoV-229E and HCoV-OC43, were identified in 1966 and 1967, respectively (Su et al., 2016). They are symptomatically indistinguishable, as infection with either virus typically results in cold-like symptoms: headaches, malaise, sore throat, etc. (Su et al., 2016). Although they both manifest in clinically identical manners, HCoV-229E and HCoV-OC43 are not directly related; HCoV-229E is an alpha-CoV whereas HCoV-OC43 is a Lineage A beta-CoV (Lau et al., 2011; Ye et al., 2020). These two community acquired HCoVs are thought to be responsible for 15% to 30% of all common respiratory tract infections (Lau et al., 2011). HCoV-OC43 and HCoV-229E occur globally, and case rates for these viruses typically spike in the winter seasons of temperate regions (Su et al., 2016; Ye et al., 2020).

The last two major community-acquired HCoVs to be discovered, HCoV-HKU1 and HCoV-NL63, were both first reported in 2004 in Hong Kong and the Netherlands, respectively (Forni et al., 2017; Su et al., 2016; Ye et al., 2020). Although HCoV-229E and HCoV-OC43 were symptomatically similar, HCoV-HKU1 and HCoV-NL63 are distinguishable by their symptoms. Symptoms associated with HCoV-HKU1 include fever, nasal discharge, dyspnea, bronchiolitis, and pneumonia (Su et al., 2016; Ye et al., 2020). Symptoms associated with HCoV-NL63 include croup, rhinorrhea, fever, conjunctivitis, bronchiolitis, etc (Su et al., 2016; Ye et al., 2020). Both HCoV-NL63 and HCoV-HKU1 are globally occurring viruses in the human population (Su et al., 2016).

Molecular Structure of SARS-CoV-2:

Figure#1A details virus entry

Figure#1B detailing S1 and S2 cellular processes

Couso, J., Patraquim, P. Classification and function of small open reading frames. Nat Rev Mol Cell Biol 18, 575–589 (2017). https://doi.org/10.1038/nrm.2017.58

The Coronavirus structure is crucial towards understanding its function and alarmingly rapid spread throughout the human population. Understanding the structure provides useful insight towards the COVID-19 compatibility with the human CD26 protein (CDC, 2019). The proteins surrounding the spherical virus proved to be pivotal towards understanding how COVID-19 interacts with humans. The surface of the virus is covered in glycoproteins or amino acid chains with carbohydrate groups attached to these chains. They are referred to as “ spike glycoprotein” due to the protruding nature of the spikes on the surface of the virus. These spikes attach to the host cell and fuse with the host’s membrane, enabling virus entry (Wrapp et al., 2020). The inside is immersed in single-stranded RNA and a HEMagglutinin-esterase protein which is a protein crucial for intracellular transport (Mousavizadeh et al., 2020). In comparison to other Viral structures, Coronaviruses contain the largest genomes (Mousavizadeh et. al., 2020.)

Each different, novel Coronavirus contains different ORF’s (abbreviated from Open Reading Frames). These are codons that contain start and stop, three-lettered codons. These ORF’s vary slightly between different conserved genes in Coronaviruses (ORF1ab, spike, envelope, membrane and nucleocapsid) (Mousavizadeh et. al., 2020.) Another differentiating factor is the slight alteration of the nucleocapsid proteins in different strains of Coronavirus (Mousavizadeh et. al., 2020.) In each membrane, the Coronavirus contains three to four viral proteins in the membrane with the most copious one being the (M) Glycoprotein (Mousavizadeh et. al., 2020.)The Glycoprotein leaves the NH2 Terminus on the outside of the virus which is an indicator of the beginning of a polypeptide signified by the free NH2 group. The glycoprotein then ends on the inside of the virus at the elongated COOH terminus which is an indicator of the end of the polypeptide chain (Mousavizadeh et. al., 2020.)

Figure #2 shows the evolution of Open Reading Frames (ORF’s and demonstrates the start and stop codon Couso, J., Patraquim, P. Classification and function of small open reading frames. Nat Rev Mol Cell Biol 18, 575–589 (2017). https://doi.org/10.1038/nrm.2017.58

Along with the (M) Glycoprotein is the (S) Spike Protein on the surface of the virus. This is the protein that constitutes the Spike Glycoprotein that the Coronavirus is infamously known for in its protruding spikes encasing the surface of the molecule. The (S) Spike Protein’s primary function is to neutralize Antibodies acting as a defense mechanism on the surface of the virus (Mousavizadeh et. al., 2020.) The (M) Glycoprotein is responsible for synthesizing virus particles inside of the virus independent of the Spike Protein (Mousavizadeh et. al., 2020.)

The spike glycoproteins are the primary source of adhesion to human cells and they assist in membrane fusion. On each surface are two subunits, S1 and S2. These two respective subunits mediate the fusion of membranes through different pathways, each occurring separately and consecutively (Wrapp et al., 2020.) Proteins on the surface known as nucleocapsid proteins are crucial to the function of the virus in itself for replicating and for mediating transfusion (Gutsche et al., 2015.) The Nucleocapsid proteins are crucial and practically a necessity towards the functioning of the virus enabling many of its daily functions such as RNA synthesis. These proteins contain the N and C terminals crucial to S1 (Wrapp et al., 2020.) The N Terminal is the RNA- binding site or NTD while the C-terminal is the dimerization domain. These are critical for oligomerization and RNA binding in a host cell.

Each spike is a trimeric protein or in this case, three proteins that are not chemically bonded to one another. The spike glycoproteins are the primary source of adhesion to human cells and assists in membrane fusion. On each surface are two subunits, S1 and S2 (Wrapp et al., 2020). These two respective subunits mediate the fusion of membranes through different pathways. There are proteins on the surface known as nucleocapsid proteins and these are crucial to the function of the virus in itself for replicating and for mediating transfusion. These proteins contain the N and C terminals crucial to S1. The N Terminal is the RNA- binding site or NTD while the C-terminal is the dimerization domain (Wrapp et al., 2020). Either NTD or the C-Terminal can serve the purpose of a place for membrane fusion and binding depending on the host cell it wants to bind to. This varies within molecules but COVID-19 primarily uses the N-domain to bind to other receptors on a host cell as do other forms of CoV’s including SARS-CoV and MERS-CoV.

When the trimeric protein structure fuses with the host membrane, its structure changes drastically (Wrapp et al., 2020). When the S1 subunit attaches to the host cell, the trimer protein discussed above becomes unstable. The destabilization of this trimer eliminates the S1 subunit and proceeds to move into the S2 subunit (Wrapp et al., 2020). This results in the trimer stabilizing again to another conformation after fusing with the host cell’s membrane. This conformation conceals the receptor binding sites and enables fusion with a host cell. The structure of the Coronavirus contains ridges that allow much more efficient and effective fusion with the membrane of its host cell which is why it is so effective in fusion with the Human Cells, its rapid spread and compatibility make it a detrimental force. The effectiveness of the Coronavirus in spreading among people is due primarily to ridges on its surface and the spike-like proteins amassed on its surface. Understanding the SARS-CoV 2019 structure enables a better understanding of possible treatment.

Treatments have been targeting the primary protease in the molecule (protein disassembling enzyme) referred to as the Mpro (Zhang et al., 2020). This enzyme is imperative towards the processing of larger polyproteins synthesized by the RNA in the virus. On the virus, there remains to be nothing less of eleven individual targeted sites on the molecule for Mpro cleavage (Zhang et al., 2020). Inhibiting the Mpro enzyme is the answer towards putting viral replication to a halt indicating how crucial this enzyme is inhibiting replication (Zhang et al., 2020). The peptidomimetic α-ketoamides was synthesized as broad-spectrum inhibitors by scientists to inhibit these primary proteases (Zhang et al., 2020.).

Epidemiology of SARS-CoV-2: (combined w/ Mechanism of infection)

The natural host of SARS-CoV-2 are bats and humans are the terminal host (Wang et al., 2020). The intermediate host of the virus are Pangolins, and they act as a reservoir for sexually immature parasites while they mature (Wang, et al., 2020). The source of infection is from other COVID-19 patients and severe patients are considered more contagious than mild cases (Jin et al., 2020). The basic reproductive values or basic reproductive ratio of infectious agents is a metric used to describe the contagiousness or transmissibility. Basic reproductive values or R0 (pronounced R naught) is almost always measured retrospectively using seroepidemiological data or theoretical mathematical models. The basic reproductive values (R0 ) of COVID-19 is two to three and a half, which means that an infected person could spread the disease to two or three people (Wang et al., 2020). The entry mechanism of COVID-19 varies depending on cellular proteases, some of which include, human airway trypsin-like protease (HAT), cathepsins and transmembrane protease serine 2 (TMPRSS2) that split the spike protein and establish further penetration changes (Cowling & Aiello, 2020). COVID-19 is placed in Category B of infectious agents. Therefore, it is described as moderately easy to disseminate, resulting in moderate morbidity rates and low mortality rates. However, it still requires the CDC’s observation (Singhal, 2020). The China National Health Commission recommends that COVID-19 be treated as a Category A infectious agent, meaning it should be considered high priority.

SARS-CoV-2 is considered a self-limiting disease and most mild cases can recover in one to two weeks (Jin et al., 2020). Symptoms often appear after the incubation period, which is around 5.2 days, but has an estimated upper limit of 14 days (Cowling & Aiello, 2020 ; Rothan & Byrareddy, 2020). COVID-19 spreads from human to human via respiratory droplets, explaining why large gatherings of people in close proximity can lead to an increased number of people contracting the virus. COVID-19 can also be transmitted before symptoms begin and from asymptomatic people, which aids in the rapid spread of the virus between humans. Infection of COVID-19 begins as a mild upper respiratory injury and can progress into a severe respiratory disease (Shereen et al., 2020). The most common symptoms are fever, fatigue, myalgia, and cough followed by sputum production, headaches, and diarrhea (Jin et al., 2020). Smoking, drinking, asthma, diabetes, cardiovascular disease, and cancer can increase susceptibility to the disease and are considered comorbidity factors (Jin et al., 2020). Elderly individuals and those with underlying comorbidities are especially vulnerable to the virus. 50 to 75 percent of cases in the elderly and individuals with underlying comorbidities were fatal, according to data from January to March 2020. However, fatality in hospitalized patients ranges from 4 to 11 percent, while the overall fatality rate is estimated to range between 2 and 3 percent (Singhal, 2020). COVID-19 shows unique clinical symptoms that target the gastrointestinal system like diarrhea. It should be noted that a low number of SARS and MERS patients had gastrointestinal issues (Rothan & Byrareddy, 2020). The virus can also progress to pneumonia, respiratory failure, and even death. While the virus has an upper incubation period of 14 days, the median time for onset of symptoms is five days, hospitalization for 7–10 days, and recovery following the second or third week of infection (Singhal, 2020). There are five categories that SARS-CoV-2 infections can fall into: asymptomatic, mild to medium, severe, critical and death (Jin et al., 2020). Nosocomial infection is a major issue with COVID-19, with many treatments for COVID-19 being high-risk factors for nosocomial transmission like intubation, bronchoscopy examination, patient transport and manual ventilation (Wang et al., 2020). To prevent the spread of the virus, face masks or face coverings are suggested (Cheng et. al, 2020). However, the efficacy of face masks protecting healthy individuals from the virus is unclear. Nevertheless, face masks are promoted because they may protect others from one’s own germs which is especially important because the virus can spread from an asymptomatic individual. A combination of face masks and proper hand hygiene has shown to reduce the transmission of the virus in communities (Cowling & Aiello, 2020).

The initial outbreak of COVID-19 was in Wuhan, China and the surrounding cities on December 8th, 2019. The first reported case in another province was on January 19th, 2020 in Guangdong. (Jin et al., 2020). By January 30, the first case in Tibet Province was reported and COVID-19 had spread to all of mainland China (Jin et al., 2020).

COVID-19 Testing:

There are the two distinct types of COVID tests, but a more detailed look shows that there are four subcategories of tests that people depend on to get a diagnosis and for further regulation. These four tests are serological tests, nucleic acid, antigen, and ancillary tests (Weissleder, et al., 2020). They each play a critical role in diagnosing COVID to the spectrum of people seeking to be tested, whether it be by detection or by tests done once a patient has been diagnosed with COVD. Before these tests can be understood, a basic comprehension of how detection is possible is crucial towards understanding how treatment relates to the structure of the virus and the human body.

For Nucleic Acid Tests, RNA is reverse-transcribed or made into DNA. This DNA is then amplified using the Polymerase Chain Reaction, which is a way to replicate the DNA strand into billions of copies of itself. This rapid replication also allows for amplification of the gene being targeted and replicated. The regions replicated vary depending on the virus. The U.S. Food and Drug Administration (FDA) and Centers for Disease Control and Prevention (CDC) decided on choosing the viral nucleocapsid N1, N2, and human RNase P gene to replicate and amplify versus how the World Health Organization recommended that individuals target and replicate the CoV-2 RNA-dependent RNA polymerase (RdRP) and envelope (E) genes (Weissleder et al., 2020). Different gene markers hold varied sensitivities towards the virus and can be crucial in its detection (Weissleder et al., 2020). These, in particular, are all markers that enable SARS-CoV-2 detection due to the acute sensitivity these replicated genes have for the virus.

Figure 1 shows Reverse Transcription Reverse Transcription Applications: Thermo Fisher Scientific — US. (n.d.). Retrieved from https://www.thermofisher.com/us/en/home/life-science/cloning/cloning-learning-center/invitrogen-school-of-molecular-biology/rt-education/reverse-transcription-applications.html

Serological tests, better known as Antibody Tests, depend on the specificity of ligands to bond to components of the host’s immune system, such as their immunoglobulin, which are commonly known as antibodies, and interleukin, and evaluate these particular proteins (Weissleder, et al., 2020.) These ligands are called “affinity ligands”, or ligands that bond with a specific antibody with a very high affinity towards the antibody. This comes with keen accuracy and specificity towards the antibody being targeted. The specificity of these ligands ensure that the information obtained is strictly for past and present exposure to SARS-CoV-2. The specificity of serological tests go so far as to differentiate infections caused by SARS-CoV-2 from other novel Human Coronaviruses. Serological testing helps determine past exposure to SARS-CoV-2, immunity in order to aid with vaccine development, and current exposure.

Antigen Tests, or Viral Tests, contain a high specificity towards a certain virus and the protein markers on a virus are indicators of its identity (Weissleder, et al., 2020). Antigen Tests only show current infection and not previous exposure unlike the Antibody Test. For SARS-CoV-2, the Nucleocapsid proteins and spike proteins on the surface of the virus are used to detect current exposure using ELISA or enzyme-linked immunosorbent assay (Weissleder, et al., 2020). The ELISA test identifies IgG and IgM antibodies in the host (Macdonald, et. al., 2020). Antibodies are created in response to a particular antigen so the detection of these antibodies can determine whether or not COVID is present. This test is done by using a nasopharyngeal swab, a medical professional inserts a cotton swab up the individual’s nose and moves the cotton swab around for about fifteen seconds (CDC, 2020).

Ancillary Tests are used for COVID patients and management of their vitals or condition. This includes various laboratory tests such as checking for cytokine storms and performing blood coagulation tests. These tests serve as regulators in order to ensure that a COVID patient is stabilized.

Drug Development:

Currently, there is no available vaccine for COVID-19. However, there is a vast number of researchers working to develop a variety of vaccines as well as restorative strategies to survive the virus. Research finds that several drugs have in vitro activity against the virus, but there is no clinical evidence that supports the efficacy and safety of any vaccines specifically against COVID-19 in humans (Kalil, 2020). However, genomic sequence information, in addition to protein structure modeling, has allowed scientists to develop a list of existing vaccinations that might have restorative potential for COVID-19.

When creating an antiviral vaccine, there are multiple categories including inactive or live-attenuated viruses, virus-like particles (VLP), viral vectors, protein-based, DNA-based, and mRNA-based vaccines. Vaccinations including a live-attenuated virus, viral vectors, inactivated virus, subunit vaccines, recombinant DNA, and proteins vaccines are being tested on animals (Li et al., 2020). Currently, a mRNA-based vaccine prepared by the US National Institute of Allergy and Infectious Diseases against COVID-19 is under phase 1 trial (Shereen et. al., 2020). However, a major concern while testing vaccines is whether or not it is ethical to give patients a placebo. It must be noted that it is not possible to accurately determine the harms of an experimental drug or vaccine without a control group (Kalil, 2020).

Due to new drug development being a long process, vaccines for other diseases are being examined for cross-resistance for COVID-19. The idea of cross-resistance was observed in China when children being vaccinated for the measles were less vulnerable to the virus (Shereen et al., 2020). However, scientists are working on long-term drug development goals for the virus that include identification of inhibitors aimed at the replication or infection processes associated with the virus (Liu et al., 2020).

Non-Vaccinal Methods of Treatment for COVID-19:

Although a vaccine is the best long-term solution for dealing with SARS-CoV-2, there are many other forms of treatment currently available. These forms of treatments can be split into two approaches: disrupting the CoV replication cycle and regulating the human immune response (Tu et al., 2020). The three main ways non-vaccinal drugs disrupt the CoV replication cycle are through interfering with genomic CoV ssRNA chain synthesis, interfering with viral proteases, and preventing viral cell entry (Li et al., 2020; Pruijssers et al., 2019; Tu et al., 2020). In terms of regulating immune response, non-vaccinal drugs have been used both to elevate and to attenuate immune responses, depending on the case (Li et al., 2020; Tu et al., 2020). For example, immunocompromised patients suffer from an excessive immune response, which can cause significant internal damage. In order to mitigate the amount of damage COVID-19 causes in these patients, immunosuppressive drugs are employed to prevent the immune system from overreacting. In the case of a patient with a weakened immune system, medical therapies and treatments are available to boost the immune response.

Disrupting CoV Replication Cycle: Interfering with Genomic CoV ssRNA Chain Synthesis

The most promising drug that disrupts genomic CoV ssRNA chain synthesis is Remdesivir (Tu et al., 2020). Remdesivir, a prodrug analogue of the adenosine nucleoside, is a type of nucleoside analogue inhibitor that interferes with CoV ssRNA chain synthesis (Li et al., 2020). Nucleoside (and nucleotide) inhibitors (NIs) are man-made analogues of their parent nucleoside/nucleotides but with their sugar molecule or heterocyclic ring altered so that the NI is dysfunctional or incompatible with the viral RNA-dependent RNA Polymerases (RdRp) (Pruijsssers et al., 2019). NIs interfere with CoV ssRNA chain synthesis through three main mechanisms.

One way they interfere is through introducing harmful mutations; since NIs are nucleosides that are modified to be dysfunctional, they mispair with other nucleosides during chain elongation, introducing harmful mutations as they incorporate into the new viral genome (Pruijsssers et al., 2019). NIs also interfere with CoV ssRNA chain synthesis by triggering premature chain termination; the incorporation of foreign nucleotides, such as NIs, into nascent viral RNA can cause the RdRp machinery to malfunction and prematurely terminate chain growth (Pruijsssers et al., 2019). Another way NIs interfere with CoV ssRNA chain synthesis is through competing with the natural population of nucleosides to decrease cellular nucleoside levels (Pruijsssers et al., 2019). This in turn leads to less available “healthy” nucleosides in the cell, which also results in premature chain termination as there are not enough nucleosides to elongate the viral ssRNA chain. Remdesivir exhibits broad spectrum antiviral activity against many types of viruses and holds significant potential in the treatment of COVID-19 (Guo et al., 2020; Li et al., 2020; Tu et al., 2020). Drug development against SARS-CoV-2 has proven difficult because of CoVs unique proofreading capabilities (Pruijsssers et al., 2019). Part of the CoV genome encodes for nonstructural protein 14 (nsp14), which serves as an exoribonuclease with 3’ to 5’ proofreading activity (Pruijsssers et al., 2019). Despite the CoV’s proofreading mechanism, Remdesivir has been shown to yield clinically positive results. Remdesivir was administered to the first patient in the U.S. reported to have COVID-19 on the 7th day of infection, and the patient’s condition improved by the 8th day (Guo et al., 2020).

Disrupting CoV Replication Cycle: Interfering with Viral Protease

Viral proteases are enzymes that are encoded for by the viral genome to cleave other viral proteins into their appropriate lengths and sizes. Interfering with or inhibiting viral protease function can decrease the overall viral expression and load in the host (Tu et al., 2020). For example, the HIV genome encodes for aspartyl protease, the enzyme responsible for cleaving the necessary proteins to create a new HIV virion (Tu et al., 2020). In order to treat AIDS, aspartyl protease inhibitors, such as lopinavir and ritonavir, are employed to decrease the viral expression and load of HIV in the host (Guo et al., 2020; Tu et al., 2020). Although the CoV genome encodes for a cysteine protease rather than an aspartyl protease, it is hypothesized that lopinavir and ritonavir can also inhibit the 3CL1 protease function in CoVs (Tu et al., 2020). Clinical studies have yielded mixed results on the efficacy of lopinavir and ritonavir in the treatment of COVID-19: some have shown that lopinavir and ritonavir improved the patient’s condition while others show no clinical benefit (Tu et al., 2020). More clinical studies are under way to determine the efficacy of lopinavir and ritonavir (Pruijsssers et al., 2019).

Disrupting CoV Replication Cycle: Preventing Viral Cell Entry

Hydroxychloroquine is one of the most promising drugs that prevents viral entry of SARS-CoV-2 into the host cell (Tu et al., 2020). Hydroxychloroquine increases the endosomal pH, making it difficult for SARS-CoV-2 virions to enter the host cell (Li et al., 2020; Tu et al., 2020). Hydroxychloroquine has shown to reduce viral load and expression of SARS-CoV-2 in in vitro testing as well, which shows promise for future clinical trials (Tu et al., 2020). However, it should be noted that, so far, clinical studies have yielded mixed results for the efficacy of hydroxychloroquine. (Tu et al., 2020)

Regulating Immune Response: Elevating the Immune Response

There are two main ways to enhance the immune response; addition of natural killer (NK) cells, and interferon therapy (Tu et al., 2020). NK cells are a class of cytotoxic T cells that play a central role in the immune response. They identify and respond to specific antigens, killing virus-infected cells before they can infect other healthy cells. NK cell therapy is currently under phase I trial in China, but researchers predict that NK cell therapy has significant potential in decreasing viral load and expression of SARS-CoV-2 (Tu et al., 2020). Interferons are a type of cytokines, or immunological agents, secreted by virus-infected cells that alert surrounding cells to heighten their antiviral defenses. Interferon therapy has shown broad spectrum antiviral activity and is predicted to decrease viral load and expression in SARS-CoV-2 (Tu et al., 2020). Clinical trials are currently underway to develop a safe and efficient interferon therapy for COVID-19 (Tu et al., 2020).

Regulating Immune Response: Attenuating the Immune Response

Intravenous Immunoglobulin (IVIG) regulates the immune system in a dose dependent manner (Tu et al., 2020). In low doses (0.2–0.4 g IVIG / kg body weight), it can be used to help treat antibody deficiencies, but in higher doses (2 g IVIG / kg body weight), IVIG displays immunosuppressive activity, as it prevents inflammatory cell growth and phagocytosis (Tu et al., 2020). IVIG has been commonly used in the fields of dermatology and neurology, and is currently undergoing clinical trials for treatment with COVID-19 (Tu et al., 2020). It shows significant promise for immunocompromised patients who suffer from exacerbated immune responses.

Public Health: Effects on Racial Minorities and Underprivileged Populations:

It is considered common knowledge that racial and ethnic minority populations face higher rates of health risks. These risks come about due to health disparities between racial and ethnic groups regarding health insurance coverage, quality of care, and access to care. For example, according to the United States Census Bureau’s report on Health Insurance Coverage in 2017, non-hispanic Whites had the lowest uninsured rate (6.3 percent), while Hispanics had the highest uninsured rate (16.1 percent) among other racial and ethnic groups (U.S. Census Bureau, 2018).

Health outcomes and disparities between racial groups are inevitably attributed to income. Lower incomes can indicate less access to medical resources and care. According to the U.S. Census Bureau, Blacks and Hispanics have had the lowest median household incomes since 1967 (U.S. Census Bureau, 2018). Therefore, racial minority status and socioeconomic status are interrelated.

Health outcomes and disparities between racial groups are inevitably attributed to income. Lower incomes can indicate less access to medical resources and care. According to the U.S. Census Bureau, Blacks and Hispanics have had the lowest median household incomes since 1967 (U.S. Census Bureau, 2018). Therefore, racial minority status and socioeconomic status are interrelated.

Figure 1. Graph showing median household incomes for different racial groups from 1967 to 2018. Retrieved from: U.S Census Bureau, Current Population Survey, 1968 to 2019 Annual Social and Economic Supplements.

It is extremely important to understand that socioeconomic status is a significant social determinant of health. For more information on how poverty impacts health outcomes, visit this page by the Office of Disease Prevention and Health Promotion: Poverty.

The global COVID-19 pandemic has made health inequities in the United States very evident (Dorn et al., 2020). In fact, African Americans and other racial minorities have been disproportionately affected by the pandemic. Deaths due to COVID-19 are disproportionately higher for African American communities. For example, according to data from January to April 2020, all but three people who died as a result of COVID-19 in St. Louis, Missouri were African American (Dorn et al., 2020). According to the official website of the city of St. Louis, African Americans now have a death rate of 84.2 percent, while Caucasians have a death rate of 42.4 percent (St. Louis City Government). In a preliminary study conducted by the CDC, compiled data from hospitals in 14 states found that 33 percent of COVID-19 hospitalizations were African American individuals, despite representing only 18 percent of the total population studied (Garg et al., 2020). In another study, death rates from COVID-19 in New York City were substantially higher for African and Latin Americans than that of Caucasians or Asian Americans (Kirby, 2020).

This evidence is not exactly surprising, as communities of color face higher rates of diseases than other communities. In fact, chronic conditions such as asthma, hypertension, kidney disease, and obesity, are more common in African American populations (Kirby, 2020). Native American populations also have higher levels of underlying health conditions, such as heart disease (Dorn et al., 2020). Cardiovascular health issues, especially those caused by viral infections such as myocarditis, lead to increased complications and risk of death due to COVID-19 (Masic et al., 2020).

Not only are communities of color disproportionately affected due to their underlying health conditions, but also due to their increased risk of exposure. According to the Economic Policy Institute, minority populations, and especially people of color, make up the majority of “essential workers” like janitors, grocery workers, and cashiers (McNicholas & Poydock, 2020). They especially make up the majority of essential workers in food and agriculture (McNicholas & Poydock, 2020). Additionally, people of color makeup 53 percent of essential workers in industrial, commercial, and residential facilities/services (McNicholas & Poydock, 2020). Unfortunately, these essential workers do not have the privilege to work remotely or from home. Also, oftentimes, working in these industries signifies a lack of health insurance, which exposes the systemic inequalities in the United States (Dorn et al., 2020). As stated by the CDC, these communities have an increased risk to contract COVID-19 due to the increased likeliness to live in more densely populated areas and housing, to use public transport more, and to work in lower service jobs without sick pay (Kirby, 2020). These communities lack “facilities to safely isolate or quarantine” (Kirby, 2020). This evidence is not only exclusive to the United States. In fact, the issue extends globally. In China, vulnerable and underprivileged populations were also disproportionately affected by COVID-19 when cases were high in January and February of 2020 (Wang & Tang, 2020).

Additionally, health promotion plays an extremely important role in public responses to the COVID-19 pandemic (Smith & Judd, 2020). Due to the digital age, health education is largely delivered through information technology and mass media. Unfortunately, the digital age negatively affects underprivileged communities more than others, which occurs due to a multi-faceted problem. E-readiness, or one’s ability to process digital/electronic information, is an extremely important sociological concept that affects how people respond to the COVID-19 pandemic. The relationship between e-readiness and public response to the pandemic is an extremely complex problem, because various factors such as age, education, and location (urban, suburban, and rural areas) can affect an individual’s e-readiness. Research shows that information technology, especially social media, leaves out those who lack access to it and those who do not use it frequently for a variety of reasons (Smith & Judd, 2020). Informative posts and messages about the pandemic, including preventative measures such as wearing masks and washing hands for at least 20 seconds, are published and promoted through information technology and the internet. This means that those with higher e-readiness can better understand these messages and are therefore more likely to take better preventative measures. Additionally, minority communities may have access to social media, but lack proper literacy skills to understand informative posts about the pandemic. Non-native English speakers also face language barriers and difficulties with translation after they have contracted COVID-19 and are hospitalized, causing increased anxiety and stress among these populations during treatment (Abuelgasim et. al., 2020). For more information on the digital divide and its effects on minorities (as well as minority child development), read these research papers: Closing the Digital Divide and its Impact on Minorities & Digital Inequality and Developmental Trajectories of Low-income, Immigrant, and Minority Children.

The COVID-19 pandemic has also disproportionately impacted minority unemployment. After state governments began implementing social distancing measures, the overall unemployment rate jumped to 14.7 percent (Fairlie et al., 2020).

Figure 2. Graph showing unemployment rates from 1948 to the spike in 2020. Retrieved from: Bureau of Labor Statistics, The Unemployment Situation, various issues retrieved from FRED, Federal Reserve Bank of St. Louis. Copyright 2020 by Peter G. Peterson Foundation.

These numbers have not been reached since the Great Depression in the 1930s (Fairlie et al., 2020). More specifically, according to April 2020 data, Latin American communities experienced much higher unemployment rates than White and African American communities. (Fairlie et al., 2020). The upper bound for the general Latinx community was over 25 percent, most likely due to an “unfavorable occupation distribution and lower skills” (Fairlie et al., 2020).

Lastly, it should be noted that public health emergencies like the COVID-19 pandemic can take a toll on individual and collective mental health of communities. People may feel more isolated and insecure during a pandemic (due to various reasons such as fear and unemployment), which can cause them to engage in unhealthy behaviors such as excessive substance use. Evidence from multiple studies shows that symptoms of anxiety and depression, as well as stress, are common responses to the pandemic (Rajkumar, 2020). These reactions may be associated with disturbed sleep (Rajkumar, 2020). A review of these studies can be found here: COVID-19 and mental health: A review of the existing literature and here: COVID-19 pandemic and mental health consequences: Systematic review of the current evidence. However, it should be noted that these studies are limited because they were conducted solely in Asia and Europe. As of now, there are no available studies on the mental health of the United States general public in the public domain. Therefore, it is not easy to analyze mental health differences between racial and ethnic groups.

However, it is predicted that minority populations are at a higher risk for mental health disturbances during the COVID-19 pandemic. This increased risk may be due to higher unemployment rates, increased risk of exposure, etc. The increased risk for mental health issues may also cause co-morbidities due to higher rates of underlying health conditions mentioned previously, such as diabetes and hypertension. For example, a study concluded that Latino sexual minority men (LSMM) in the Miami Area (an HIV spot) had very significant changes in mental health and substance abuse (Harkness et. al., 2020). Most of them reported increased anxiety, depression, loneliness, and alcohol use after the outbreak began (Harkness et. al., 2020). Though this group represents such a small part of the population, the majority of the group reported these symptoms.


Conclusions and Perspectives:

As cases of Coronavirus continue to increase, global efforts are focused on increasing the efficacy of testing and drug research and development. The current SARS-CoV-2 outbreak has led to innovations in modern pharmaceutical and biological technologies, also showing the impact of policy on community health. While no vaccine has been approved, there have been major strides by research teams focusing on cross-resistance. However, public discourse and adherence to public policy have been major determinants in the course of the 2020 pandemic.

The biological structure of SARS-CoV-2 shows similarity to past viruses, giving greater insight into how CoV interacts with the human genome. In relation to treatment and drug development, this has proved difficult as antiviral vaccines require live testing. Through the span of COVID-19, multiple treatments options have arised in hopes to help the most hard-hit immunocompromised individuals.

With a high rate of community infection, the COVID-19 pandemic has shown structural flaws in our public health systems, with minority communities facing the brunt of this pandemic, but has also shown scientific commitment to steady and safe vaccine development. While the future of this pandemic is unknown, the data has become more accurate, leading to greater public awareness of preventative measures in hopes to return to “normal” once again.

Conflict of Interests:

The authors declare no conflict of interests.

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Vindegaard, N., & Benros, M. E. (2020). COVID-19 pandemic and mental health consequences: Systematic review of the current evidence. Brain, behavior, and immunity, S0889–1591(20)30954–5. Advance online publication. https://doi.org/10.1016/j.bbi.2020.05.048

Wang, Y, Wang, Y, Chen, Y, Qin, Q. (2020) Unique Epidemiological and Clinical

Wang, Z., Tang, K. Combating COVID-19: health equity matters. Nature Medicine, 26, 458(2020). https://doi.org/10.1038/s41591-020-0823-6

Wong, L. R., Lui, P., & Jin, D. (2016). A molecular arms race between host innate antiviral response and emerging human coronaviruses. Virologica Sinica, 31(1), 12–23. https://doi.org/10.1007/s12250-015-3683-3

Wrapp, D., Wang, N., Corbett, K. S., Goldsmith, J. A., Hsieh, C., Abiona, O., . . . Mclellan, J. S.

https://www.thermofisher.com/us/en/home/life-science/cloning/cloning-learning-center/invitrogen-school-of-molecular-biology/rt-education/reverse-transcription-applications.html

Figure 2. Graph showing unemployment rates from 1948 to the spike in 2020. Retrieved from: Bureau of Labor Statistics, The Unemployment Situation, various issues retrieved from FRED, Federal Reserve Bank of St. Louis. Copyright 2020 by Peter G. Peterson Foundation.

These numbers have not been reached since the Great Depression in the 1930s (Fairlie et al., 2020). More specifically, according to April 2020 data, Latin American communities experienced much higher unemployment rates than White and African American communities. (Fairlie et al., 2020). The upper bound for the general Latinx community was over 25 percent, most likely due to an “unfavorable occupation distribution and lower skills” (Fairlie et al., 2020).

Lastly, it should be noted that public health emergencies like the COVID-19 pandemic can take a toll on individual and collective mental health of communities. People may feel more isolated and insecure during a pandemic (due to various reasons such as fear and unemployment), which can cause them to engage in unhealthy behaviors such as excessive substance use. Evidence from multiple studies shows that symptoms of anxiety and depression, as well as stress, are common responses to the pandemic (Rajkumar, 2020). These reactions may be associated with disturbed sleep (Rajkumar, 2020). A review of these studies can be found here: COVID-19 and mental health: A review of the existing literature and here: COVID-19 pandemic and mental health consequences: Systematic review of the current evidence. However, it should be noted that these studies are limited because they were conducted solely in Asia and Europe. As of now, there are no available studies on the mental health of the United States general public in the public domain. Therefore, it is not easy to analyze mental health differences between racial and ethnic groups.

However, it is predicted that minority populations are at a higher risk for mental health disturbances during the COVID-19 pandemic. This increased risk may be due to higher unemployment rates, increased risk of exposure, etc. The increased risk for mental health issues may also cause co-morbidities due to higher rates of underlying health conditions mentioned previously, such as diabetes and hypertension. For example, a study concluded that Latino sexual minority men (LSMM) in the Miami Area (an HIV spot) had very significant changes in mental health and substance abuse (Harkness et. al., 2020). Most of them reported increased anxiety, depression, loneliness, and alcohol use after the outbreak began (Harkness et. al., 2020). Though this group represents such a small part of the population, the majority of the group reported these symptoms.

Conclusions and Perspectives:

As cases of Coronavirus continue to increase, global efforts are focused on increasing the efficacy of testing and drug research and development. The current SARS-CoV-2 outbreak has led to innovations in modern pharmaceutical and biological technologies, also showing the impact of policy on community health. While no vaccine has been approved, there have been major strides by research teams focusing on cross-resistance. However, public discourse and adherence to public policy have been major determinants in the course of the 2020 pandemic.

The biological structure of SARS-CoV-2 shows similarity to past viruses, giving greater insight into how CoV interacts with the human genome. In relation to treatment and drug development, this has proved difficult as antiviral vaccines require live testing. Through the span of COVID-19, multiple treatments options have arised in hopes to help the most hard-hit immunocompromised individuals.

With a high rate of community infection, the COVID-19 pandemic has shown structural flaws in our public health systems, with minority communities facing the brunt of this pandemic, but has also shown scientific commitment to steady and safe vaccine development. While the future of this pandemic is unknown, the data has become more accurate, leading to greater public awareness of preventative measures in hopes to return to “normal” once again.

Conflict of Interests:

The authors declare no conflict of interests.

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Ahmad Ibsais

I am a first-generation Palestinian-American, student, and youth activist fighting for human rights, healthcare equality, and climate justice.