What is COVID-19?

What are Viruses?

Microorganisms are biological entities that are generally too small to see with the naked eye. Microorganisms are found everywhere; many are harmless to humans, but some are pathogenic meaning they can cause disease. Viruses are a type of microorganism comprised of genetic material (DNA or RNA) enclosed in a protein coat (capsid) and sometimes a lipid envelope (fatty membrane). Viruses are acellular, meaning that they lack the cellular structures needed to replicate by themselves and must use a host cell making them an intracellular parasite. This makes virus different from other types of microorganisms such as bacteria, which are single-celled organisms that contain the cellular machinery needed to divide and grow independently both in hosts and on surfaces (Willey, Sherwood and Woolverton, 2011).  

Novel Coronavirus SARS-CoV-2

In December 2019, an outbreak of pneumonia with no known origin began in China, which was soon discovered to be caused by a new virus that had not caused illness in humans before (World Health Organization [WHO], 2020a). The novel virus was named Severe Acute Respiratory Syndrome-Related Coronavirus (SARS-CoV-2) (Coronaviridae Study Group, 2020) and the disease it causes was named Coronavirus Disease 2019 (COVID-19) (WHO, 2020b).

COVID-19 Symptoms 

SARS-CoV-2 infects the respiratory tract of humans. The virus causes damage to the cells and results in an immune response (inflammation) which causes the symptoms of COVID-19. COVID-19 can range in severity, from mild to fatal. It is thought that about 80% of people who develop COVID-19 have mild to moderate symptoms, 14% have severe symptoms and 6% develop very severe (critical) symptoms. There is also evidence that some people who contract the virus do not show any symptoms but can transmit it to other people (European Centre for Disease Prevention and Control [ECDC], 2020a).

After exposure to the virus, there is an incubation period before symptoms appear, this is usually around 5-6 days but can range from 1-14 days (ECDC, 2020a). The most common symptoms of COVID-19 are similar to the flu, with a fever and cough. Shortness of breath, a sore throat, tiredness, muscle aches and headaches are also common symptoms (Gaythorpe et al., 2020). In more severe cases, patients may develop pneumonia, where the air sacs (alveoli) of the lungs become inflamed and fill with fluid. In critical conditions acute respiratory distress syndrome can develop, where widespread inflammation prevents the lungs from delivering enough oxygen to the bloodstream, which can be fatal (Public Health England [PHE], 2020a). Sepsis is another potentially fatal complication of COVID-19, where the body’s immune response to the infection causes organ and tissue damage. The fatality rate of COVID-19 in the UK and EU is currently estimated to be 5.4%, with a greater risk of death in older people and those with pre-existing conditions (e.g. high blood pressure and diabetes) (ECDC, 2020a).

SARS-CoV-2 Structure

SARS-CoV-2 belongs to the coronavirus family, a group of viruses that are known to cause infections of the respiratory tract, central nervous system and gastrointestinal tract of mammals and birds. Coronaviruses are large, spherical viruses that carry a genome of positive-sense single-stranded RNA as their genetic material. The RNA genome is encased in a protein capsid followed by a lipid envelope (fatty membrane) with spike proteins protruding from the surface (Fehr and Perlman, 2015; Chen et al., 2020). 

SARS-CoV-2 Replication 

Viruses including SARS-CoV-2 needs to enter a host cell to replicate. Viruses enter the cell by attaching to a specific receptor on the surface of the host cell and transferring their genome into the cell. SARS-CoV-2 is believed to attach to host cells by the viral spike proteins binding to an enzyme on the surface of host cells called Angiotensin-Converting Enzyme 2 (ACE2) (Zhang et al., 2020). Once attachment has occurred, the lipid envelope of coronaviruses fuse with the host cell membranes allowing the virus to enter the cell. The host cell’s machinery is used to make new copies of the virus using the viral RNA as a template. The new virus particles are then transported out of the cell (Fehr and Perlman, 2015).   

SARS-CoV-2 Hosts

Coronaviruses are known to cause disease in humans, a range of other mammals and birds and have been shown to jump between species (zoonotic transmission) (Chen et al., 2020). Zoonotic transmission can occur by handling infected animals or consuming infected animal products (Willey, Sherwood and Woolverton, 2011). Bats are host to several coronaviruses that are genetically similar to those found in humans. The genome of SARS-CoV-2 is 96% similar to the RATG13 coronavirus found in bats, suggesting that they could be the original reservoir of SARS-CoV-2 (Zhou et al., 2020). It is hypothesised that SARS-CoV-2 jumped from bats to an intermediate host animal before humans, where human-to-human transmission then began (Andersen et al., 2020). Some studies show that the pangolin harbours coronaviruses similar to SARS-CoV-2 (Xiao et al., 2020) but they are not similar enough to be considered a direct ancestor, so the intermediate host is currently unknown. Another hypothesis is that the virus jumped to humans before it was able to cause illness, and then in humans evolved to cause COVID-19 (Andersen et al., 2020). 

SARS-CoV-2 Taxonomy

SARS-CoV-2 is a member of the Coronaviridae or coronavirus family (Coronaviridae Study Group, 2020). The name coronavirus comes from the Latin corona, meaning crown, because spike proteins protrude from surface of the virus like a crown. There are four genera within the Coronaviridae: Alphacoronavirus and Betacoronavirus, which generally infect mammals, and Gammacoronavirus and Deltacoronavirus which infect birds and fish in addition to some mammals. SARS-CoV-2 belongs to the genera Betacoronavirus, which also contains closely related coronaviruses severe acute respiratory syndrome coronavirus (SARS-CoV), which was responsible for an outbreak of severe respiratory disease (SARS) in 2002-2003, and Middle East respiratory syndrome coronavirus (MERS-CoV) which was first reported in 2012 (Chen et al., 2020). 

Diagnosis of COVID-19

COVID-19 is diagnosed by identifying the SARS-CoV-2 virus in patients. Swabs are usually taken from the back of the nose and throat and a sample of sputum (mucus) from coughing is obtained. The samples are placed in tube containing viral transport media, a solution that keeps the virus alive during transport to the testing laboratory (PHE, 2020a; WHO, 2020c). 

The samples are analysed using real-time reverse-transcription polymerase chain reaction (rRT-PCR), a molecular technique that detects the presence of specific genes in the virus RNA (WHO, 2020c). This is achieved by converting the RNA into DNA and then amplifying it so that there is enough to be detected by the PCR machine. 

rRT-PCR begins by separating the viral RNA from the rest of the sample. The RNA is added to a mixture of enzymes and chemicals and placed in the PCR machine.

RNA is first converted into DNA by the enzyme reverse transcriptase by heating to 55°C. In the melting stage, the sample is heated to 95°C to melt any double stranded DNA into single strands and then cools to 60°C. Next is the annealing stage, where short pieces of DNA with a complementary sequence to the virus gene (primers) bind to the DNA, along with a fluorescent probe. The primers are recognised by an enzyme called DNA polymerase, priming it to start copying the gene (amplification). During amplification, DNA polymerase breaks down the fluorescent probe, which produces a fluorescent signal. The PCR machine goes through 40 cycles of melting, annealing and amplification, doubling the number of copies of the gene each time. Eventually enough copies will be present to produce a fluorescent signal strong enough to be detected by the PCR machine. If the virus is not present, there will not be any amplification and little to no fluorescent signal would be detected (Corman et al., 2020).

Scientists are also working on developing simple, rapid ‘point-of-care’ tests to detect COVID-19 in under 1 hour. In the UK, COVID-19 testing is conducted mainly on hospitalised patients; patients that have more mild cases are not routinely tested (PHE, 2020b). Tests to determine if a person has previously had COVID-19 and recovered are currently being researched, which would help scientists understand the disease. These tests would detect the presence of IgM and IgG antibodies specific to SARS-CoV-2 present in the blood, which are immune proteins that develop during the course of infection and provide immunity to future infection (Long et al., 2020).

Treatment of COVID-19

There are currently no specific treatments available for COVID-19. Treatment is currently based on relieving symptoms, including taking antipyretics, drugs that lower a fever, e.g. paracetamol (NHS, 2020). Oxygen can be administered to help keep oxygen blood levels normal in more severe cases. In critical cases, patients are put on a ventilator, a machine that moves air in and out of the lungs, because the patient cannot breathe sufficiently by themselves (ECDC, 2020b).

Antivirals are a type of drug that treat viral infections by stopping the virus from replicating (Finch et al., 2012). There are no antiviral drugs currently available to treat coronaviruses. Antivirals are challenging to develop because viruses use host cells to replicate. The antiviral must target the virus without affecting host cell functions, otherwise it would be toxic to humans. This limits the structures of the virus that can be targeted for development of new drugs (Adalja and Inglesby, 2019). Antivirals are different from antibiotics, which are drugs that treat bacterial infections. Antibiotics do not work against viral infections because they target structures specific to the bacterial cell, which are not present in viruses. 

Antivirals generally target only one specific type of virus so currently available antivirals may have limited to no effect on COVID-19 infections. Research is being conducted to find current antiviral drugs that might be repurposed to treat COVID-19. For example, the HIV drugs lopiniavir and ritonavir were tested in COVID-19 patients in China but did not improve the condition of the patients (Cao et al., 2020). Other possible treatments include pegylated interferon alfa-2a and -2b, which stimulate human cells to produce natural antiviral responses (Lu and De Clerq, 2020). Hydroxychloroquine (an autoimmune disease drug) was shown to prevent SARS-CoV-2 from entering the host cell in laboratory studies (Liu et al., 2020) and improved recovery times of COVID-19 patients in a small clinical trial; larger clinical studies are needed to fully evaluate its effects (Chen et al., 2020). 

What is COVID-19? Resources

Brainpop (2020) Coronavirus [Online] Available from: https://www.brainpop.com/health/diseasesinjuriesandconditions/coronavirus/ [Accessed 06/04/2020].

• Video explaining SARS-CoV-2 and the COVID-19 outbreak, with associated quiz, worksheets, related reading and vocabulary. General virology videos and resources are also available.

Exploratorium (2020) How Does Soap Inactivate Coronaviruses? [Online] Available from: https://www.exploratorium.edu/video/how-does-soap-inactivate-coronaviruses [Accessed 06/04/2020]. 

• Video explaining how the SARS-CoV-2 lipid envelope is inactivated by soap and alcohol.

Medley, G. (2020) Coronavirus: A Book for Children [Online] Available from: https://nosycrowcoronavirus.s3-eu-west-1.amazonaws.com/Coronavirus-ABook... [Accessed 08/04/2020]. 

• Book explaining what COVID-19 is to children.

Microbiology Society (n.d.) Viruses [Online] Available from: https://microbiologysociety.org/why-microbiology-matters/what-is-microbi... [Accessed 06/04/2020].

• Introduction to viruses and their replication for teachers, with links to information and podcasts on specific viruses.

Microbiology Society (n.d.) Resources [Online] Available from: https://microbiologyonline.org/students/resources-1 [Accessed 06/04/2020]

• Microbiology teaching resources, including practical investigations, fact files on specific diseases and comics for KS2 and KS3.