SARS (Severe Acute Respiratory Syndrome): A Tale of Two Deadly Viruses

History

SARS-CoV-1

The Severe Acute Respiratory Syndrome Coronavirus 1 (SARS-CoV-1) is believed to have been transmitted to humans from animals in open-air markets in China [8]. The first outbreak occurred in November 2002 in the Guangdong province of Southern China. 

But, the first officially confirmed case was reported in Hong Kong in February 2003. An infected medical doctor who came from the Guangdong province infected around sixteen people who came in contact with him in Hong Kong, including his brother‐in‐law and a few healthcare workers [9].

Later in the year, Malik Peiris, a Hong Kong-based virologist, isolated the SARS-CoV-1 virus for the first time [10]. In the same year, the disease caused by the pathogen was given the name “Severe Acute Respiratory Syndrome (SARS)” by WHO [9].

SARS-CoV-2

Almost 16 years after the SARS outbreak, ‘a new coronavirus was discovered. The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) was identified in Wuhan, China, in December 2019 and soon began spreading to different parts of the world [11]. WHO declared it a public health emergency of international concern in January 2020 [3]. 

In February 2020, the new virus was named ‘SARS-CoV-2’, and the disease was called “COVID-19”. The term ‘COVID-19’ stands for ‘Coronavirus Disease 2019’. The virus spread fast across the globe and was declared a pandemic on 11th March 2020 [12]. 

By the end of 2020, there were over 150 vaccine development projects running to combat the pandemic. Fifty of them went through clinical trials, and a few were administered to the general population[13]. As of May 2022, over 300 COVID-19 vaccines were either in the preclinical or clinical development stages, and around ten vaccines received approval from the WHO for global use.

Epidemiology

Some of the common coronaviruses that cause severe respiratory illnesses in humans include SARS-CoV-1, SARS-CoV-2, and MERS-CoV. MERS-CoV causes Middle East Respiratory Syndrome (MERS) [12]. They belong to the subfamily Othocoronavirinae of the family Coronaviridae [15].

SARS-CoV-1 

SARS-CoV-1 infection or SARS spread to different parts of the world, covering over 30 countries (including China and Hong Kong) on five continents. Hong Kong and China (and its special administrative regions) were most affected, accounting for around 87% of all cases and 84% of all SARS-related deaths worldwide [9]. 

By mid-2003, only a few cases were being reported, including those acquired in laboratories. This was followed by a small outbreak that occurred in early 2004 [16]. At the end of the epidemic, there were 8,422 reported cases and 916 deaths – which is around 10% of all reported cases [17].  

SARS affected people of all age groups. Most of the infected people were healthy individuals between the age group of 25 and 70 years. There were also a few suspected cases of the disease reported among children under 15 years of age [4]. 

SARS-CoV-2

The SARS-CoV-2 virus was first isolated from a patient who was admitted to a hospital in Wuhan, China, on 26th December 2019 [18]. It then spread to 228 countries and territories, disrupting the lives of millions of people across the planet [19]. As of today, over 625 million COVID cases and over 6.5 million deaths have been reported worldwide, according to WHO. 

Unlike SARS, which occurred predominantly in Asia, COVID-19 wreaked havoc around the globe, with Europe and the Americas accounting for over 50% of reported cases. Countries badly affected by the pandemic include the United States, India, France, Germany, Brazil, South Korea, and the UK, to name a few. The US remains one of the worst affected countries and has reported over 95 million cases and over one million deaths. It is closely followed by India, which reported over 44 million cases and half a million deaths. If we compare COVID-related deaths alone, the US tops the list, followed by Brazil and India [2]. 

People over 60 years of age or those with underlying health issues like diabetes, weak immune system, or heart or lung diseases are at a higher risk of developing severe illness due to SARS-CoV-2 infection [20].

How is it spread?

Both SARS CoV-1 and SARS CoV-2 are highly infectious and can spread from one person to another through direct or indirect contact. 

• Direct contact: Coronaviruses can be spread by inhaling respiratory droplets released into the air when an infected person talks, coughs, or sneezes. The concentration of these respiratory droplets in the air is high within a radius of 3 to 6 feet from an infected person. 
• Indirect contact: Touching contaminated surfaces and then touching the mouth, nose, or eyes with contaminated hands can also spread the disease [1,21].

Biology of the disease

Coronaviruses have spiky proteins on their surface that give the virus the appearance of a crown. In fact, the name ‘Coronavirus’ stems from the latin word for crown, ‘corona.’ These viruses have been seen in many hosts, including humans, bats, birds, and more. SARS-CoV-2 rapidly mutated into several variants and sub-variants that had their own unique ways of circumventing our immune systems. 

SARS-CoV-1

The SARS-CoV-1 virus enters the body through the respiratory tract and primarily affects the epithelial cells in the lungs. The virus also enters macrophages (specialized cells that destroy bacteria and other harmful substances) and dendritic cells (that boost our immune response). However, while the virus cannot replicate in these cells, it stimulates them to release inflammation-fighting cytokines and chemokines into the bloodstream. As the immune response continues, this ‘storm’ of cytokines can result in the collapse and malfunction of the lungs [22].

SARS-CoV-2

The COVID-19 virus enters the body through the respiratory tract and attacks cells in the lungs (alveolar epithelial Type 2 or AT2) cells. These cells play an essential role in maintaining the stability of the lungs. The spike proteins on the surface of SARS-CoV-2 bind to ACE2 receptors on the AT2 cells in the lung. SARS-CoV-2 also binds to ACE2 receptors on endothelial cells, enterocytes (in the intestine), heart, kidney, and pancreas. 

Once the virus enters a host cell, it produces and disseminates copies of the virus. It also stimulates macrophages, causing them to release cytokines and chemokines into the bloodstream, similar to SARS-CoV-1. This release results in the dilatation of blood vessels and the movement of blood plasma in and out of the capillaries. The leaked plasma accumulates around AT2 cells and compresses them, leading to alveolar collapse and malfunctioning of the lungs. As a result, the infected individual may experience difficulty in breathing, low oxygen levels, and cough. 

Cytokines released into the bloodstream also affect the brain’s hypothalamus, and body temperature rises. In severe cases, the abnormal inflammatory responses can cause septic shock, multi-organ failure, and death [23].

Symptoms

SARS-CoV-1

It can take two to seven days for the symptoms to appear following exposure to the virus. Initial symptoms include:

• High fever (over 100.4°F) – sometimes accompanied by chills and rigors
• Headache
• Body and muscle pains
• Fatigue
• Diarrhea (less common) [1,24]

After three to seven days, people experience:

• Dry cough
• Shortness of breath
• Tightness in the chest
• Decrease in blood oxygen levels [24].

SARS-CoV-2

It can take two to fourteen days for the symptoms to appear following exposure to the virus. The most common symptoms include:

• Fever and chills
• Dry cough
• Fatigue
• Loss of smell and taste

Other less common symptoms include:

• Sore throat
• Body and muscle pains
• Headache
• Nausea or vomiting
• Diarrhea
• Rashes
• Discoloration of fingers or toes

Serious symptoms that require immediate medical attention:

• Breathing difficulty
• Chest pain
• Loss of speech or mobility
• Confusion [25,26]

SARS-CoV-2 had several variants and sub-variants, and the incubation period for each of them varied. The Omicron BA.5 variant, for example, has an incubation period of 5 days. 

Diagnosis

SARS-CoV-1

Different diagnostic methods exist to detect the presence of the SARS virus in humans, including RT-PCR, viral culture, and serologic tests. 

• RT-PCR: It is an effective method to detect genetic material of the infectious agent in blood, stool, and nasal secretions.
• Serologic testing: It is used to detect the presence of antibodies to an infectious agent in the blood. 
• Viral culture: It is done by placing an infected tissue or fluid in a container where the virus can grow. Cell changes seen under a microscope are used to confirm the presence of the infectious agent [27].

SARS-CoV-2

According to the CDC, there are two commonly used methods to detect the presence of SARS-CoV-2. They are:

• Rapid Antigen Tests: Rapid Antigen Tests (RATs) were widely used during the SARS epidemic and COVID-19 pandemic. Since test results can be available within 15 to 30 minutes of testing, they were useful in frontline screening and at-home self tests. However, they are less reliable compared to NAAT (including RT-PCRs). If a RAT test result is negative, experts advise taking a follow-up test after 48 hours to make sure [36].
• Nucleic Acid Amplification Test (NAAT) or PCR: NAAT is more reliable compared to other testing methods that are available. They can detect the presence of genetic material of the virus. But, it is not advisable to take up NAAT if you have tested positive for COVID-19 in the last 3 months as the genetic material of SARS-CoV-2 can remain in the body for up to 3 months. 

Treatment

SARS-CoV-1

There is no effective treatment for SARS. Testing is underway to identify an antiviral drug that would effectively treat the disease. The CDC recommends that people with SARS be given the same treatment used to treat community-acquired atypical pneumonia [28].

SARS-CoV-2

Antiviral and antibiotic drugs are available to reduce the severity of the infection and prevent deaths. For the treatment to be effective, it has to be started as early as possible following the onset of the symptoms. 

The good news is there are a few antiviral drugs (Nirmatrelvir with Ritonavir, Remdesivir, and Molnupiravir) and monoclonal antibodies (Bebtelovimab) approved by the FDA to treat mild to moderate infections. These antiviral drugs help slow down the replication process of the virus, and antibodies help the immune system effectively fight against the virus [29]. 

With mass vaccination drives and as the SARS-CoV-2 continued to mutate, symptoms of COVID-19 became milder leading to fewer COVID-19-related hospitalizations and deaths. 

Eventually, for the Omicron BA.4 and BA.5 subvariants, CDC guidelines were to isolate at home for five days.

Prevention

There are no vaccines available to protect against SARS-CoV-1 [30]. But, different SARS-CoV-2 (COVID-19) vaccines are available for the general population. They are found to be effective in reducing the severity of the disease and preventing hospitalizations and deaths [31]. 

Here are a few of the COVID-19 vaccines approved by WHO for general use: 

• Inactivated virus vaccines: They are usually the first choice of vaccines for new infectious diseases. This is because they are easy to make and are efficient in triggering humoral immune responses [32]. Some examples include Sinopharm’s Covilo, Sinovac’s CoronaVac, and Bharat Biotech’s Covaxin [14].
• mRNA vaccines: mRNA vaccines are considered much safer as they are designed to enter the cytoplasm of a cell to generate target antigens as opposed to DNA vaccines that have to enter the nucleus of target cells to stimulate antibody production [32]. Some examples include Moderna’s Spikevax mRNA-1273 and Pfizer–BioNTech’s Comirnaty BNT162b2 [14].
• Adenovirus vector-based vaccines: These non-replicating viral vector vaccines are usually very effective in most individuals except for people with recessive infectious viruses [32]. These types of vaccines have no freezing requirements and can be used in developing countries where the temperature is warm. Examples include AstraZeneca’s Vaxzevria and Covishield ChAdOx1 and Johnson & Johnson’s Janssen’s Ad26.COV2 [14].
• Adjuvanted protein vaccines: These are available under emergency use authorization and are given to people over 12 years [33]. Some examples include Novavax’s Nuvaxovid and Covovax NVX-CoV2373 [14].

However, vaccine effectiveness wanes over time, and booster shots are recommended. Booster shots were updated in 2022 to cover Omicron subvariants BA.4 and BA.5, the dominant strains at the time. [31].

Other infectious disease preventive measures that can help contain the spread (of SARS-CoV-1 and SARS-CoV-2) include:

• Maintaining physical distancing of about one meter from other people – especially in public places.
• Wearing gloves and face masks in public places – especially where physical distancing is not possible.
• Washing hands regularly using soap.
• Keeping the house and the rooms properly ventilated.
• Covering the mouth and nose while sneezing or coughing.
• Cleaning and disinfecting the surfaces – floors, walls, furniture, etc.
• Avoiding places that have or recently had a coronavirus outbreak.
• Self-isolating for a few days following exposure to infected people or those suspected to be infected [21,34,35].

Many eagerly anticipated the COVID-19 vaccine rollout as the best way to control the pandemic, but some expressed scepticism. Overall, COVID-19 vaccinations did not prevent infections from occurring, but helped minimize COVID-19-related hospitalizations and deaths [31, 35]. 

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