COVID-19 - A clinical update

Coronaviruses infect many species of animal including the bat. These RNA viruses frequently mutate particularly in bats, and chance mutations rendered the SARS-CoV-2 capable of readily infecting humans. The bat virus infected an intermediate host, possibly the Pangolin that was sold in the live fish and animal market in China. A key virulence (characteristic that allows a pathogen to cause disease) factor is the S protein which was the likely primary target of the mutations. This protein forms knobs on the outer surface of the virus that bind strongly to the ACE2 receptor on human respiratory epithelial cells. Binding is followed by internalization and within the cell the virus replicates its RNA using a replicase and assembles into a nuclear capsid in the host cell cytoplasm RNA is also translated into proteins that coat the outer surface of the virus. Once fully assembled the virus is exocytosed (released) from vesicles. The new viral particles can infect other cells and spread to other humans. Because of the inaccuracy of the viral replicase as the virus actively grows it produces point mutations. Some of these mutant virus more effectively infect cells. The alpha variant became prominent in the Winter and Spring of 2021 subsequently a more highly infectious variant the Delta variant that originated in India dominated and now a third variant, omicron that originated in South Africa is now spreading throughout the world and quickly dominating in Europe and the U.S. The virus first replicates in the throat and nasal passages and then spreads to the trachea, bronchi and alveoli where it induces inflammation and damage to the alveolar walls causing fluid to leak into the air exchanging sacks and interfering with oxygen exchange. If inflammation continues the alveolar walls become fibrosed (scarred) and further compromising oxygen exchange resulting in decreases in oxygen saturation (hypoxia). SARS-CoV-2 is able to spread efficiently from person to person primarily by droplets and aerosol (tiny particles that stay in the air for hours). Infection quickly spread throughout the world and caused a pandemic within 3 months. Humans were infected at the Huanan live fish and animal market. The infection initially was confined to workers in the market (point source) but then quickly spread person to person within the first 10 days. Because of the lack of travel restrictions early in the outbreak Chinese traveling from the area quickly spread the virus to many other countries. In the early phases lack of therapy or vaccine allowed the virus to move from person to person unchecked with a steep exponential curve with a doubling of cases every 2-3 days. This virus is one of the most infectious ever reported each infected person on average infecting 2.0 to 2.7 people, the alpha variant can infect 3.0-5.0, the Delta variant one person on average infects 5-8 individuals and the omicron 10-16. The last two variants can cause breakthrough infections in vaccinated individuals. Another characteristic that has allowed rapid spread is the existence of 40-60% asymptomatic or minimally symptomatic carriers. 10% are superspreaders infecting on average 10-80 others.