Epidemiology of COVID-19 caused by SARS-CoV-2 as of March 29, 2020

Last Updated on September 6, 2020 by Sagar Aryal

Some viruses, including human coronavirus OC43 (HCoV-OC43), contain a third glycoprotein (HE; 65 kDa) that causes hemagglutination and has acetylesterase activity.

The viral structural proteins include a 50–60 kDa phosphorylated nucleocapsid (N) protein, a 20–35 kDa membrane (M) glycoprotein that serves as a matrix protein embedded in the envelope lipid bilayer and interacting with the nucleocapsid, and the spike (S) a 180–220 kDa glycoprotein that makes up the petal-shaped peplomers.

There are 20 nm long club or petal-shaped projections that are widely spaced on the outer surface of the envelope, suggestive of a solar corona.

The helical nucleocapsid is 9–11 nm in diameter.

The large, plus-stranded RNA genome associates with the N protein to form a helical nucleocapsid.

Coronaviruses are enveloped, 120 to 160 nm particles that contain an unsegmented genome of single-stranded positive-sense RNA (27–32 kb).

Figure: Structure of Coronavirus, created with biorender.com

Each subgenomic mRNA and the viral genomic RNA, which also serves as an mRNA, is translated to yield only the protein encoded by the 5′ gene on the mRNA.

Coronavirus-infected cells contain multiple overlapping subgenomic, capped, and polyadenylated mRNAs with a common 3′ end.

This IS sequence is essential for the formation of subgenomic RNAs.

In the genome, a common intergenic sequence (IS) of about 7 bases is found at the 5′ end of each gene.

Coronavirus genomes also include a variety of additional open reading frames (ORFs) that encode two to four nonstructural proteins of unknown functions.

The order of the genes encoding the viral RNA-dependent RNA polymerase and the four common structural proteins, the spike (S), envelope (E), membrane (M), and nucleocapsid (N) proteins are indicated as Pol-S-E-M-N.

The replicase gene products are encoded within two very large open reading frames, ORFs 1a and 1b.

The 5′ approximately 20 to 22 kb carries the replicase gene, which encodes multiple enzymatic activities.

Coronavirus genomes are monopartite, single-stranded, positive-sense, polyadenylated, and capped RNAs ranging from 27 to 32 kb in length.

The incidence of coronavirus infections varies markedly from year to year, ranging in one 3-year study from 1% to 35%.

The contribution of each HCoV may vary widely from year to year, for example, 229E contributing as little as 1% to acute respiratory infections in the community in one year and up to 35% in the next.

Studies using virus detection or serology have shown that HCoV 229E, OC43, and NL63 occur worldwide.

It is estimated that coronaviruses cause 15–30% of all colds.

Natural outbreaks of colds caused by coronaviruses occur predominantly during the winter months, although in children, two peaks in late autumn to early winter and early summer were detected.

SARS-CoV-2 could transmit from one human to another human.

A novel coronavirus known as SARS-CoV-2 was identified in Wuhan, China when people developed pneumonia-like symptoms.

Epidemiology of COVID-19 caused by SARS-CoV-2 as of March 29, 2020

Epidemiology of COVID-19 caused by SARS-CoV-2 as of March 29, 2020

Figure: Replication of Coronavirus, created with biorender.com

Natural infection of humans with human respiratory coronaviruses occurs through exposure to respiratory secretions.

Coronaviruses attach to their glycoprotein receptors on host cells via their S proteins.

Viral entry is mediated by fusion of the viral envelope with the host cell membrane or by receptor-mediated endocytosis.

Group 1 coronaviruses 229E and NL63 bind to the metalloproteases, human aminopeptidase N and angiotensin-converting enzyme 2 (ACE-2) respectively.

The receptors for OC43 and HKU-1 have not been yet identified.

The fusion of the viral and cell membranes (either at the cell surface or within the endocytic vesicle) is mediated by the S2 portion of the virus spike protein which functions as a class 1 fusion protein.

Once the viral RNA is released into the cytoplasm, translation of the positive-strand genomic RNA gives rise to a large polyprotein that undergoes proteolytic processing to generate an RNA-dependent RNA polymerase.

An RNA-dependent RNA polymerase translated from the plus-stranded viral genomic RNA makes a negative-strand that serves as the template for a nested set of five to seven subgenomic mRNAs.

Translation of subgenomic mRNAs gives rise to structural viral proteins.

The N protein and newly synthesized genomic RNA assemble to form helical nucleocapsids.

Membrane glycoprotein M is inserted in the endoplasmic reticulum (ER) and anchored in the Golgi apparatus.

The nucleocapsid (N plus genomic RNA) binds to M protein at the budding compartment (ERGIC).

E and M proteins interact to trigger the budding of virions, enclosing the nucleocapsid.