Coronavirus: The Past, Present and Future

Coronavirus is defined to be a group of viruses that causes respiratory disease in birds and mammals. In humans, infection from this virus can result in flu-like symptoms including fever, cold, cough and diarrhea. Coronaviruses are characterized by club-like spikes that project from their surface [1] and are named after the latin word Corona which means ‘crown’ or ‘halo’.

There are currently seven known strains of human coronaviruses (HCov): HCov-229E, HCoV-OC43, HCoV-NL63, HKU-1, SARS-CoV, MERS-CoV and 2019-nCov. The first four strains are responsible for the common cold and result in mild to moderate respiratory infections that circulate the human population world-wide [2]. Human coronaviruses can cause lower-respiratory tract illnesses in people with weakened immune systems, infants and the elderly, leading to pneumonia or bronchitis [3].

SARS

SARS-CoV, the fifth coronavirus strain, was the pathogen involved in the SARS global outbreak of 2002–2003 which infected 8,437 people worldwide with 813 deaths. SARS (Severe Acute Respiratory Syndrome) is an infectious respiratory disease with significant morbidity and mortality [4].The strain was first reported in Guangdong Province of China, but quickly spread to countries in North America, South America, Europe and Asia [5]. Affected patients presented flu-like symptoms including fever, chills, cough and malaise [6]. Approximately 70% of patients subsequently suffered from shortness of breath and recurrent or persistent fever [7].

All strains of coronavirus, including SARS-CoV, spread in an air-borne manner through close animal-to-person or person-to-person contact. Virus particles have been isolated in sputum samples, nasal secretions, and bronchial washings [8, 9] suggesting that SARS-CoV is transmitted by close contact and/or droplets [10, 11]. It’s now widely accepted that SARS-CoV originated in Chinese horseshoe bats. When studied, these bats contained sequences of SARS-related CoV’s and serologic evidence for a prior infection with a related CoV [12, 13].

MERS

Middle Eastern Respiratory Virus, or MERS-CoV for short, is a strain of coronavirus that is the causative agent of a severe and frequently fatal acute respiratory illness somewhat resembling SARS-CoV [15]. The strain originated from the Arabian Peninsula and affected residents of the Middle East, Africa and South Asia in 2012. Initial symptoms are often non-specific and patients reported general malaise with low-grade fever, chills, headache, cough, dyspnea and myalgia [16, 17]. There is evidence that MERS-CoV stemmed from dromedary camels (Camelus dromedaries); direct or indirect human contact with the camels resulted in the virus spreading into the human population [18]. MERS is very contagious with a high mortality rate (~35%). The 2012 outbreak of MERS infected 2,494 people and killed 858 [19].

nCoV-2019

The latest coronavirus, nCoV-2019 or Wuhan Coronavirus, is the causative agent for acute respiratory disease and the ongoing 2019–2020 Wuhan Coronavirus Outbreak. The virus was first detected (and believed to be originated) in Wuhan, China but has now spread to Europe, United States, Asia and Australia. Patient presenting symptoms include fever, cough, diarrhea, dyspnea and sore throat with over half suffering with shortness of breath and pneumonia [27].

Early cases have been linked to a local fish and live animal market, and since coronaviruses are zoonotic in nature, they can easily spread from animal-to-people and then people-to-people [28]. Snakes or bats are the most likely animal hosts of nCoV-2019, which infected other animals who then transferred the virus to the human population [29]. The nCoV-2019 strain allows for asymptomatic transmissions through children and young people, unlike SARS. These transmissions would have been very difficult to detect since health officials are identifying individuals with visible symptoms. According to the National Health Commission of the People’s Republic of China, as of January 31st, the cumulative number of confirmed cases was 11,791 and 259 deaths [30].

Disease Parameters

Control of an outbreak relies partially on identifying what the disease parameters are and how each parameter can help contain the virus. Three important parameters are the Reproductive number (R0), Fatality rate (CFR) and Incubation period.

• The R0 is the average number of secondary cases generated by a primary case and if R0 > 1, an epidemic typically occurs [20].

1. The reproductive number for SARS-CoV was estimated to be between 2 and 3 but based on locations which outbreaks occurred, R0 was approximately 3. [21].
2. R0 for MERS-CoV was first thought to be <1 [22] but based on recent findings, R0 for nosocomial infections in Saudi Arabia and Korea (greatest number of casualties) is between 2 and 5 [23].
3. Initial findings calculated R0 for nCoV-2019 to be between 2.0 and 3.1 [31, 32].

• The case fatality rate, which measures the likelihood that a disease will kill its host, is an important indicator of the severity of a disease [24].

1. CFR for SARS-CoV is between 14–15% according to the World Health Organization.
2. CFR for MERS-CoV is estimated to be 34.4% according to the World Health Organization.
3. CFR for nCoV-2019 is between 2–3% [33].

• Incubation period is the time from exposure to a causative agent to onset of disease. This parameter is important since it forms the basis for many recommended control measures including contact tracing, duration of home isolation for probable patients and physician diagnosis [24].

1. Current and previous findings support the conclusion that the maximum incubation period for SARS-CoV is 10 days.
2. The Center for Disease Control indicate incubation period for MERS-CoV is 5 days [25].
3. The director of China’s National Health Commission indicates the incubation period of nCoV-2019 as 10–14 days however, the United States Center for Disease Control estimates incubation between 2–14 days [34].

Coronavirus Outbreak Status and Analysis

Bar Graph showing each country affected with the number of infected individuals and the death toll for SARS-CoV

Scatterplot showing the Infection and Death Timeline for SARS-CoV

The first (bar graph) and second graph (scatterplot) above show SARS-CoV virus data from the World Health Organization. The bar graph details each country affected, the number of infected people and the death toll in each country overall. China had the greatest number of infections (5,327 people) and (348) deaths. The scatterplot shows the infection and death rate timeline for SARS-CoV from first recorded occurrence in March 2003 (21 infected, 1 death) to peak in June 2003 (8403 infected, 775 death) and end in July 2003.

Bar Graph showing each country affected with the number of infected individuals for MERS-CoV

Scatterplot showing the Infection and Death Timeline for MERS-CoV

The third (bar graph) and fourth graph (scatterplot) above show MERS-CoV virus data from the World Health Organization. The bar graph details each country affected and the number of people infected from 2012 to 2019. Saudi Arabia had the greatest number of infections, 2111 people. The scatterplot shows the infection and death rate timeline for MERS-CoV from first recorded occurrence in September 2012 (1 infected, 0 deaths) and latest December 2019 (2494 infected, 858 deaths).

Bar Graph showing each country affected with the number of infected individuals and the death toll for nCoV-2019

Scatterplot showing the Infection and Death Timeline for nCoV-2019

The fifth (bar graph) and sixth graph (scatterplot) above show nCoV-2019 Coronavirus data from the National Health Commission of the People’s Republic of China. The bar graph details each country affected so far, the number of people infected and the death toll in each country overall. China had the greatest number of infections (11901 people) and (259) deaths. The scatterplot shows the infection and death rate timeline for nCoV-2019 from first recorded occurrence in Dec 31st 2019 (41 infected, 0 deaths) and latest Jan 31st 2020 (~12,000 infected, 259 deaths).

As the shapes of the timeline graphs for SARS, MERS and nCoV-2019 differ greatly, we cannot conclude an infection pattern for n-CoV based on SARS or MERS. We can only make predictions using nCoV-2019 data.

Scatterplot predicting the number of affected individuals in mid-February 2020

The seventh graph (scatterplot) takes into account the dates and number of infected individuals. The shape of the graph is characterized by strong curvature and was best fitted using a third order polynomial curve. R2 of this graph is 0.977 indicating that the data fit quite well to the model. Extrapolating this model for an extra 10 days, which is when experts believe the virus will peak, revealed that about 43,000 individuals would be infected by February 10th 2020. As the Case Fatality Rate is between 2–3% as per the World Health Organization, the range of deaths would be between 860–1290 based on this model. Then, the number of people infected and succumbed to death per day is likely to stabilize and then taper off.

This model was created in Microsoft Excel to analyze, but with more data machine learning algorithms would be equally effective in pattern-recognition. Machine learning could also be of great use in predicting infectious disease outbreaks before they occur; BlueDot AI did just this for the n-CoV 2019 outbreak one week before the Center for Disease Control did. Kamran Khan, the founder and CEO of BlueDot AI which is a health monitoring platform from Canada, said in a statement that BlueDot picked up ‘news of possible outbreaks, little murmurs or forums or blogs or indications of some kind of unusual events going on’ [38]. Their algorithm uses machine learning and natural language processing to detect signs of potential disease outbreaks from the collected information, which is then verified by an epidemiologist.

Coronavirus Precautions & Containment

SARS was contained in human populations in 2003 and MERS in 2013 largely by aggressive use of traditional public health interventions such as case finding & isolation, quarantine of close contacts and enhanced infection control measures [26].

Many efforts are being made to combat the effects of nCoV-2019. Airports across the world are screening passengers for coronavirus symptoms such as fever, cough and malaise. Several domestic and International flight carriers including Delta, American Airlines, British Airways, Air India and Lufthansa have reduced or cancelled flights to and from China and Hong Kong. Scientists across the world are trying to create a vaccine for the new virus which will enter clinical trial testing in a couple months, hoping to prevent such an epidemic in the future. In China, authorities have transportation on lockdown, quarantined millions of people and closed schools/workplaces. The individual person should take precautions; do not travel to China or the affected areas, avoid close contact with anyone who has a cough or fever, avoid direct unprotected contact with live animals if you go to a live market, do not consume raw or undercooked animal products [37].

Update: (2/11/2020)

My 10-day prediction (from Feb 1-Feb 10) was extrapolated from the scatterplot graph which takes into account the dates and number of infected individuals beginning late December 2019. Comparing the predicted graph values to the actual values reported by the National Health Commission of the People’s Republic of China, as shown in the table below, we can see that the rate of infection has not yet peaked. From the SARS and MERS trajectories, we know that once the virus peaks, the number of infections & deaths will stabilize and then slowly taper off. At this time, we don’t know when the virus will peak, stabilize or taper. In the last ten days, the difference between the total actual infected cases and the total projected infected cases is less than 4%, translating to the mathematical accuracy of the projected model.

News about the coronavirus has spread widely over the last ten days, providing great awareness to individuals and showcasing the serious situation in China and the affected countries. Measures have been taken by people all over the world, from governments to businesses to scientists to individuals. Infected people have been swiftly quarantined, transportation lines including cruise ships & airplanes have taken appropriate action, and scientists across the world are working on developing drugs & vaccines to contain the outbreak.

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