Understanding COVID-19 and some Effective Means for Combating it!

By: Ziad O. Abu-Faraj, Ph.D., Professor of Biomedical Engineering

First Published: March 29, 2020.

Keywords: COVID-19, Coronavirus, SARS-CoV-2, Pandemic, Flattening the Curve, Non-pharmaceutical Interventions

Synopsis: This article discusses the nature of the Coronavirus disease, a.k.a. COVID-19, which is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It begins by addressing its etiology, morphology, transmission, pathogenesis and related symptoms. It then refers to some important facts related to the global outbreak of this pandemic. The article then delves into effective means—both interventional and nonpharmaceutical interventions—employed in combating this disease, generally around the world and particularly in mainland China, including the urgent quest for new treatment drugs and vaccine. Lastly, the article closes with a discussion about COVID-19 and some concluding remarks.

The COVID-19 Coronavirus

The World Health Organization describes COVID-19 or Coronavirus disease as an infectious disease caused by a newly discovered coronavirus [1]. Coronaviruses are a group of related viruses that cause diseases in mammals and birds [2]. In humans, coronaviruses (HCoVs) cause respiratory tract infections that can be mild, such as some cases of the common cold, and others that can be lethal, such as SARS-CoV, MERS-CoV, and COVID-19 [2]. SARS-CoV (Severe Acute Respiratory Syndrome - Coronavirus) was first identified in Foshan municipality, Guangdong Province, China, in November 2002, as the cause of an outbreak of severe acute respiratory syndrome [3]. On July 5, 2003, the World Health Organization declared severe acute respiratory syndrome contained [4]. MERS-CoV first identified in Saudi Arabia in 2012 as the cause of Middle East respiratory syndrome [3, 5]. COVID-19 is a coronavirus identified as the cause of coronavirus disease 2019 (COVID-19) that started in Wuhan, Hubei Province, China in December 2019, and spread worldwide [3]. Later COVID-19 was confirmed as novel coronavirus on January 7, 2020 [6]. Figure 1 shows an electron microscope image of an isolate from a U.S. case of COVID-19.

Figure 1. An electron microscope image of the Novel Coronavirus SARS-CoV-2, also known as 2019-nCoV, the virus that causes COVID-19. The image was made available by the U.S. National Institutes of Health in February 2020. Source: ? The National Institute of Allergy and Infectious Diseases - Rocky Mountain Laboratories via AP.

Early cases of COVID-19 were linked to a live animal market in Wuhan, Hubei, China, suggesting that the virus was initially transmitted from animals to humans [3]. Person-to-person spread occurs via contact with infected secretions, mainly through close contact with large respiratory droplets generated when an infected person sneezes or coughs; however, it could also occur through contact with a surface contaminated by respiratory droplets or other fomites [3]. The National Institutes of Health reported that the virus can live on surfaces up to 72 hours: in aerosols for up to three hours, up to four hours on copper, up to 24 hours on cardboard, and up to two to three days on plastic and stainless steel [7].

According to the World Health Organization, most people infected with the COVID-19 virus will experience mild to moderate respiratory illness and recover without requiring special treatment [1]. However, older individuals, and those with underlying medical problems such as chronic respiratory disease, cardiovascular disease, diabetes, and cancer are more prone to develop serious sickness [1].

Coronaviruses are large pleomorphic spherical particles with bulbous surface projections [8]. The diameter of the virus particles is around 120 nm [9]. The envelope of the virus in electron micrographs appears as a distinct pair of electron dense shells [10]. Figure 2 shows a conceptual model of a cross-section of Coronavirus.

In general, when a virus particle gains maturity, its behavior becomes controlled by the proteins that form the exterior structure of the virus [11]. In the coronavirus, two of these proteins—membrane (M-Protein) and envelope (E-Protein)—form the shell of the virus. A third protein is the spike protein (Spike Glycoprotein), which creates the corona (crown) around the virus which lends it its name, and serves to latch on to the living cells to enable infection. In some coronavirus strains, the envelope protein can be eliminated without prohibiting the virus from infecting cells, the fact that makes it a useless target for therapies [11]. Also, the membrane protein is the most abundant protein on the surface of the virus, but it is small and buried within the membrane. Hence, not much of it is accessible to the outside environment. Combine that with the fact that it does not appear to have any enzymatic function, makes it a non-ideal therapeutic target, either [11]. That leaves the spike (glyco)-protein, a complicated protein that offers a wealth of targets for possible therapies. As the most prominent feature of the virus' exterior, the spike protein is the main target of antibodies against the virus produced by the immune system [11].

Figure 2. A conceptual cross-sectional model of a Coronavirus. Adapted from: https://www.scientificanimations.com/wiki-images/

The COVID-19 gains entry into the body through the eyes, nose, or mouth. Once in the body, the virus starts replicating itself efficiently and spreads throughout at a massive rate. It then grips onto the human cells by binding its spike glycoproteins to Angiotensin Converting Enzyme 2 receptors or ACE2 receptors on the cell membrane of normal cells, especially those in the lungs. Specifically, the viral proteins enter into the human cells through their ACE2 receptors. Once inside, the coronavirus captures the healthy cells and takes over command and, eventually, destroy some of the healthy cells [12, 13]. At the beginning of the infection, an infected person produces a large quantity of the virus; however, this person does not exhibit any symptoms since the incubation period of the infection is 5.1 days as recent research shows [14]. However, according to the US Centers for Disease Control and Prevention these symptoms may appear 2-14 days after exposure based on the incubation period of MERS-CoV viruses [15]. Accordingly, the infected person is inadvertently able to carry on his/her life as normal and, hence, contributes to the spread of the virus [14]. COVID-19 presents in three patterns of infection: i) it begins with mild illness and upper respiratory tract symptoms, ii) this is followed by non-life-threatening pneumonia, and iii) after about a week, severe pneumonia with acute respiratory distress syndrome can progress rapidly and sometimes require life support [14]. When infected, the body triggers a cytokine response whereby immune cells attack the virus. In certain cases and for yet undefined reasons, the virus may trigger an over reactive response from the immune system, which can further dampen recovery efforts [14].

Common symptoms of COVID-19 include fever, cough, and shortness of breath. Other symptoms may include muscle pain, sputum production, diarrhea, sore throat, and abdominal pain [15, 16]. While the majority of cases result in mild symptoms, some progress to pneumonia and multi-organ failure [17]. As of March 28, 2020, the overall rate of reported deaths per number of diagnosed cases is 4.66 percent as calculated from the numbers reported by the Center for Systems Science and Engineering (CSSE) at Johns Hopkins University [18]. 

The Global Outbreak of the COVID-19 Pandemic

The outbreak of COVID-19 was declared a Public Health Emergency of International Concern on January 30, 2020 [19]. On March 11, 2020, WHO officially announced COVID-19 as a pandemic [19].

In about ten weeks from first being identified in Wuhan, Hubei, China, in December 2019 [19], China was able to combat and contain the COVID-19 to a stable manageable level by resorting to serious measures that include different tasks, the highlights of which are: declaration of a state of emergency, mass surveillance and big data, total isolation of cities and provinces, lockdowns, massive disinfection campaigns, identification of genetic sequence for COVID-19, etc. On March 10, 2020, Chinese President Xi Jinping vows victory over coronavirus while addressing patients and medical workers at the Huoshenshan Hospital in Wuhan through a video conference [20]. On March 28, 2020, the number of confirmed cases in mainland China plateaued at around 81,996 cases [18].

As the epicenter of COVID-19 moved primarily to Italy and Iran [18], preventative measures were hindered because of several factors, mainly the undermining of the potency of COVID-19 and its ability to spread fast. By the time that semi-appropriate measures were taken by neighboring countries—for instance to ban flights from China, Italy, Iran, and other countries with high rates of confirmed cases—it was a bit late! Iran became one of the global epicenters of the coronavirus [21]—especially for the Middle East region—and Italy, Spain, Germany, France, et al. made Europe the new world’s epicenter for COVID-19 [22].

The first case of COVID-19 was confirmed in the United States on January 20, 2020 [23]. On March 18, 2020, the number has risen to 6,496 confirmed cases and is exponentially rising [18]. On March 28, 2020, this number reached 104,837 taking the lead of all confirmed cases in the world! [18].

As of March 5, 2020, Italy deployed emergency field hospitals to fight COVID-19 [24], but till March 17, 2020 there were no tangible progress, instead more of disappointment and drop of morale within the relentless healthcare givers that became desensitized to day-night cycle. On March 28, 2020, the number of confirmed cases in Italy has risen to 86,498 [18], and the rate of confirmed cases infected with COVID-19 is still not showing any signs of decline!

Figure 3 shows a COVID-19 Global Cases for three consecutive days of March 27-29, 2020 as provided by the Center for Systems Science and Engineering (CSSE) at Johns Hopkins University, Baltimore, MD, USA.

Figure 3. COVID-19 Global Cases as of March 27-29, 2020. Source: Center for Systems Science and Engineering (CSSE) at Johns Hopkins University.

Combating the COVID-19 Pandemic

Several healthcare authorities such as WHO, CDC, NIH, ECDC, and many other governmental agencies and private biotechnology and pharmaceutical companies have been racing to find vaccines and medicines to fight against COVID-19 [25]. While these companies are responding faster than ever to emerging health threats, efforts to develop vaccine for COVID-19 have to course through a relatively long process before they become reliable. Today, there are claims that although “we must urgently develop measures to tackle the new coronavirus — but safety always comes first” [25]. Figure 4 shows how biotech companies are responding faster to emerging health threats.

Recent research has capitalized on a large body of knowledge pertaining to coronaviruses that have long caused significant diseases in domesticated animals raised in an agricultural setting, and so SARS-CoV-2 does not arrive as a complete unknown. As a matter of fact, the world is in an adequate position to understand what might produce a good potential therapy for COVID-19 [11]. There is currently no treatment precisely approved for COVID-19, and there is no cure for an infection caused by this disease. Instead, treatment focuses on managing symptoms as the virus runs its natural course [26].

Figure 4. Months from viral genetic-sequence selection to first human study. Source: ? Bio, Washington, DC, USA.

Anderson et al. describe that a crucial matter for epidemiologists is assisting policy makers on making a choice for the main objectives of mitigation; such as, “minimizing morbidity and associated mortality, avoiding an epidemic peak that overwhelms health-care services … and flattening the epidemic curve to wait for vaccine development and manufacture on scale and antiviral drug therapies.” The authors state that such mitigation objectives are, however, hard to attain by the same interventions; accordingly, choices must be made about priorities [27]. Figure 5 illustrates the concept of Flattening the Epidemic Curve.

Figure 5. Flattening the Epidemic Curve. Source: Centers for Disease Control and Prevention.

In April 2017, the US Centers for Disease Control and Prevention published an article by Quall et al. about the community mitigation guidelines to prevent pandemic influenza [28]. The authors state that “When a novel influenza A virus with pandemic potential emerges, nonpharmaceutical interventions (NPIs) often are the most readily available interventions to help slow transmission of the virus in communities, which is especially important before a pandemic vaccine becomes widely available. NPIs, also known as community mitigation measures, are actions that persons and communities can take to help slow the spread of respiratory virus infections, including seasonal and pandemic influenza viruses” [28].

Categories of nonpharmaceutical interventions (NPIs) also known as community mitigation strategies include the following guidelines [28]: i) personal protective measures for everyday use (e.g., voluntary home isolation of ill persons, respiratory etiquette, and hand hygiene); ii) personal protective measures reserved for influenza pandemics (e.g., voluntary home quarantine of exposed household members and use of face masks in community settings when ill); iii) community measures aimed at increasing social distancing (e.g., school closures and dismissals, social distancing in workplaces, and postponing or cancelling mass gatherings); and, iv) environmental measures (e.g., routine cleaning of frequently touched surfaces).

Using the natural laws of engineering described by the solution of a linear non-homogeneous differential equation of first order, Figure 6 shows an estimation of the safe distance for avoiding cross-infection from a person with COVID-19, which follows a decaying exponential function with a space constant of 5 meters. The ordinate of this graph reflects the percent chance of cross-infection for a particular distance in meters away from the infected person which is shown on the abscissa of the graph.

Figure 6. An estimation of the safe distance for avoiding cross-infection from a person with COVID-19.

The term R0, R nought or R zero, describes how many cases of a disease an infected person will go on to cause [29]. R0 for COVID-19 has been reported as R0 = 2.2 (95% Confidence Interval 1.4-3.9) [30]. Given an incubation period of 2-14 days [15], Figure 7 (Top) illustrates the effect of cross infection with a hypothetical R0 = 3.0 from one person at level 1 (2-14 days) in four different levels yielding 3 cross-infections at level 2 (days 4-28), 9 at level 3 (days 6-42 days), and 27 at level 4 (days 8-56). Hence, a total of 40 infected individuals are infected in a period of 56 days from the onset of the first infection. Figure 7 (Bottom) illustrates the effect of social distancing on cross infection from one person at level 1 (2-14 days) in four different levels; however, person 3 at level 2 and person 6 at level 3 decided to isolate themselves resulting in 3 cross-infections at level 2 (days 4-28), 6 at level 3 (days 6-42), and 14 at level 4 (days 8-56). Hence, the total number of infected individuals has been reduced to 24 individuals infected during the same period of 56 days from the onset of the first infection. 

Figure 7. Top: The effect of cross infection with a hypothetical R0 = 3.0 from one person at level 1 (2-14 days) in four different levels yielding 3 cross-infections at level 2 (days 4-28), 9 at level 3 (days 6-42), and 27 at level 4 (days 8-56). Bottom: The effect of social distancing on cross infection from one person at level 1 (2-14 days) in four different levels; however, person 3 at level 2 and person 6 at level 3 decides to isolate themselves resulting in 3 cross-infections at level 2 (days 4-28), 6 at level 3 (days 6-42), and 14 at level 4 (days 8-56).

On March 13, 2020, Lai et al. stated that the containment strategies of the COVID-19 outbreak in China based on non-pharmaceutical interventions (NPIs) appeared to be effective [31]. The authors added that quantitative research is still needed, however, to evaluate the effectiveness of different candidate NPIs and their timings so as to steer ongoing and future responses to epidemics of this novel disease around the World. In their study, the authors developed and validated a travel network-based susceptible-exposed-infectious-removed (SEIR) model in order to simulate the outbreak of COVID-19 across cities in mainland China. The authors employed historical and near-real time human movement data—obtained from Baidu location-based service—to calculate the intensity of travel restrictions and contact reductions across China. The results of this study were as follows: it is estimated that there were a total of 114,325 COVID-19 cases in mainland China as of February 29, 2020. These were highly correlated (p < 0.001) with reported incidence. The authors state that without NPIs, the number of COVID-19 cases would likely have shown a 67-fold increase, with the efficacy of different interventions varying. They then say that the early detection and isolation of cases was estimated to avert more infections than travel restrictions and contact reductions; however, combined NPIs would achieve the strongest and fastest effect [31].

The authors continue to state that “If NPIs could have been conducted one week, two weeks, or three weeks earlier in China, cases could have been reduced by 66%, 86%, and 95%, respectively, together with significantly reducing the number of affected areas. However, if NPIs were conducted one week, two weeks, or three weeks later, the number of cases could have shown a 3-fold, 7-fold, and 18-fold increase across China, respectively” [31]. Results also recommend that the social distancing intervention ought to be sustained for the next few months in China so as to prevent case numbers from increasing again, particularly after travel bans were lifted on February 17, 2020. The authors conclude their article by stating that the NPIs deployed in China seem to be successfully containing the COVID-19 outbreak, nevertheless the effectiveness of the different interventions varied, with the early case detection and contact reduction being the most effective. They add that deploying the NPIs early on is also imperative to prevent further spread. They recommend that early and combined NPI strategies should be prepared, adopted and adjusted to diminish health, social and economic impacts in affected regions around the World [31].

Discussion and Conclusions

Monitoring the global numbers of confirmed COVID-19 cases for the past weeks, makes one realize that the current measures, whether interventional or non-pharmaceutical interventions, employed today mainly in North America, Central and South America, Europe, Western Asia, Australia, and Africa are important but insufficient, particularly in the U.S., Italy, Spain, Germany, France, and Iran according to published data on Coronavirus COVID-19 Global Cases by the Center for Systems Science and Engineering (CSSE) at Johns Hopkins University, Baltimore, MD, USA [18]. It seems that there are relentless attempts to fight the symptoms but not the disease... Aside from the published non-pharmaceutical interventions measures followed in the aforementioned countries, efforts to contain the spread of COVID-19 ought to focus on massive use of disinfectants and other more potent measures such as those tested in mainland China. Figures 8-9 show massive disinfection campaigns performed in mainland China to eradicate COVID-19.

Figure 8. Fighting COVID-19 in mainland China by massive disinfection campaigns. Source: Unknown.

Figure 9. Massive disinfection of cities in mainland China against COVID-19 outbreak. Source: China Central Television (CCTV, Beijing, China).

Furthermore, the Chinese government employed the highest-tech epidemic control to combat the COVID-19 virus. Using mass surveillance and big data, the Chinese government collected enormous amounts of data about its citizens and used them in novel ways to tackle the coronavirus, Figure 10 [32]. About 200 Million images captured in real-time from CCTV cameras used face recognition and other biometrics to track individuals using a central database and data analytics, Machine Learning (ML), and Deep Learning (DL). The Chinese government used another big source of data to track individuals, monitor their messages, and the goods they are buying through WeChat, the multi-purpose messaging, social media and mobile payment app [32]. If one travels to China and gets admitted to the hospital because of COVID-19 symptoms, the hospital will register with the authorities and the authorities will pull down the name of the person from their database. Then, through ML and DL algorithms, they can determine all the different places that this person has been to for the last 14 days and all of the people that this person might have been in contact with. These individuals would then be notified that they have to self-quarantine for the next 14 days [32]. Additionally, the Chinese government has promoted social solidarity and framed it as the people’s war against the virus in social media and e-billboards [32]. Around 20,000 medical workers flew into Wuhan to help contain the crisis. Doctors, both males and females, have shaved their heads so as to minimize the possibility of carrying and transmitting the virus showing their commitment to social solidarity [32]. 

Figure 10. Mass surveillance of people movement in mainland China using big data analytics. Source: Journal of Democracy, Washington, DC, USA.

In conclusion, while the world is witnessing a historic socio-economic and health crisis, there are still positive sides to this ordeal. Using simple engineering concepts, what is being faced today is a transient response of a natural phenomenon. There will be some time needed to reach a plateau. Inevitably, many people will fall victims of this pandemic before it is over. Once plateaued, life will resume gradually to its normal, however, with lessons to learn. In the aftermath, Countries and Nations united should reflect back on the COVID-19 pandemic and highlight the points where they have failed and those where they have succeeded. It is important to keep in mind that the COVID-19 pandemic viciously infected humans without any prejudice as to their geographic location, education, socioeconomic status, political beliefs, race and ethnicity, religion, gender, age, abilities or disabilities, national origin, and other factors. A word of appreciation has to be extended to all the medical workers and volunteers for their relentless and non-selfish efforts in helping those in most need. Perhaps, the greatest benefit of this ordeal is that our planet “Earth” has taken a break to recover from decades of abuse!

Acknowledgment

This work was supported by funds from Stars of Science, Khayal Production - Qatar Foundation, Qatar Science and Technology Park, Tech 1 - 1st Floor, P.O. Box: 5825, Doha, Qatar.

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