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SARS-CoV-2: What You Should Know.

The SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2) is the cause of the on-going coronavirus disease-2019 (Covid-19) that has infected more than 100 million people and has claimed more than 2.5 million lives. It has crippled the world economic systems – more people live in abject poverty than ever before! Today, we summarise what you should know about the virus. We shall enrich our selves with knowledge about how the virus replicates, the virus particle, and viral entry. We shall also look at the body’s immune response to the virus.

Doctors first identified SARS-CoV-2 among patients with peculiar community-acquired pneumonia in Wuhan, China, in December 2019. Scientists think the virus originated from bats. In January, scientists were able to sequence the genome of the virus and made it public. Scientists used the information to innovate messenger RNA (mRNA) vaccines and other novelties.

SARS-CoV-2 is a single-stranded RNA virus with a genome that comprises 29000 bases. It is the lengthy genome when compared to other the known RNA viruses. It implies that there are many potential sites for the virus to mutate during the replication process. It is important to note that the virus does not interact with the host cell’s genome.

SARS-CoV-2 genome compared to other RNA viruses
SARS-CoV-2 genome compared to other RNA viruses.
Credit: NEJM Knowledge+
SARS-CoV-2 particle
Image Credit: NEJM Knowledge+

The virus particle comprises a core of a single-stranded RNA associated with a nucleocapsid (N) protein. Surrounding it is a membrane that has an envelope (E) protein, spike (S) proteins, and a membrane (M) protein. The spike protein has two subunits: S1 and S2. The S1 subunit contains a receptor-binding domain that recognises and binds to the host receptor angiotensin-converting enzyme-2 (ACE2). Meanwhile, the S2 subunit mediates viral cell membrane infusion. We can visualise these proteins under an electron microscope, arranged like a crown. The coronavirus family attains its name for this reason.

As noted above, the virus uses the ACE2 receptor to enter the host cell. ACE2 is an enzyme that is attached to the cell membranes of various cells. It counteracts the effects of a sister enzyme ACE by inactivating angiotensin II.

ACE2 interacts with the spike protein to allow viral entry into the host cell
ACE2 interacts with the spike protein to allow viral entry into the host cell Credit: NEJM Knowledge+

Regardless of its long genome, SARS-CoV-2 has a lower overall mutation rate than other RNA viruses. It has an enzyme (exonuclease) that proofreads the viral genome during replication. When mutations occur, the new viral variants can either be highly infectious or attain an exceptional ability to evade the host immune system even when the host has received a vaccine. It is worth noting that these variants mostly occur by chance.

The most widely spread variant is the D614G. The two other variants are B.1.1.7 and B.1.351. B.1.1.7 was initially in the UK: B.1.351 was in South Africa. They have since spread across the globe.

When the virus enters the human body, the immune system releases proinflammatory cytokines by the innate immune system. They include interleukin-1 (IL-1), interleukin-2 (IL-2), interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-α), and interferon-gamma.

SARS-CoV-2 interacts with the host cell.
SARS-CoV-2 interacts with the host cell.
credit: NEJM Knowledge+

 

 

SARS-Cov-2 entry ignites the immune system to release cytokines.
SARS-Cov-2 entry ignites the immune system to release cytokines.
Image credit: NEJM Knowledge+

 

 

 

 

 

 

When these cytokines are released, they attract T cells. The T cells then promote B cell differentiation that culminates in antibody synthesis and release. In a few patients, the immune response induces a cytokine storm that leads to a cascade of an inflammatory process from which acute respiratory distress syndrome (ARDS) develops. The receptor-binding domain of the spike protein plays a vital role in promoting immunity.

Due to SARS-CoV-2, the cytokines attract T cells and B cells
Credit: NEJM Knowledge+

Almost immediately after an infection, SARS-CoV-2 antibodies (Ig M and Ig G) levels begin rising. They then slightly decrease over time but can remain detectable up to 8 months following an infection. The more severe the disease is, the higher the antibody titres. In a few cases, especially mild Covid-19, the antibodies can be undetectable even after laboratory confirmation of the infection.

There’s evidence of an antibody-mediated immunity as the recurrence of covid-19 is reportedly uncommon. The presence of antibodies may confer at least a short-term immunity. However, no one knows yet how long – or to what extent are people with antibodies protected against reinfection. Also, no one knows what concentration of antibodies is required to confer such protection. But current evidence suggests that relatively low antibody titres may be protective.

Note: Information about SARS-CoV-2 and Covid-19 is ever-changing as more research papers are published. The information that appears in this article is current at the time of publication. It is from a training program about Covid-19 Vaccines currently being taught at the NEJM Knowledge+. You can enrol and take the CME for free from here. Lastly, all images are the property of the respective owners.

 

IAmDrSsekandi

Dr A. M. Ssekandi is a medical officer, researcher, content creator, author, and founder of ssekandima.com. He does private practice with a public touch. He is a certified digital marketer. He has earned certificates in Understanding Clinical Research and Writing in Sciences from the University of Cape Town and Stanford University respectively. He also has a certificate of Good Clinical Practice from https://gcp.nidatraining.org/

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