Thursday, June 11, 2020

Ch 1. A war within - Immunity to coronaviruses in context of COVID-19

Chapter 1
Reading time: 1:43 minutes
Readability: Grade 8

Novel coronavirus SARS-Cov2 has ravaged the world with the COVID-19 pandemic. The purpose of this series is to highlight the many ways the virus and the immune system engage in war games. We will uncover espionage, understand intricate diplomacy as the virus and cells interact. We will flinch at unforgiving brutality and the bizarre consequences of a struggle to prevail.

Coronavirus (like any other viruses) lives inside human cells. Initial site of infection and home for the virus are the cells lining the respiratory tract. ACE2, a protein on surface of special lung cells (type 2 cells) allows virus to bind to cell surface. This protein is important for our health, and the virus latches on, to its advantage. Once the virus makes home inside the lung cells, it starts multiplying.
Fig 1. A Trojan horse: virus uses our protein to get inside the cells
The infected cells begin to look ill, with a change in expression of proteins on surface. These 'danger patterns' signal for attention and are a cue for immune system to respond. While the flags are being put up to raise an alarm, infected cells try and limit this enemy from within. To reduce virus spread, infected cells make proteins (called interferons) to block virus functions. These interferons boost the protective defenses of other, non-infected cells. A successful interferon response should suppress viral infection at an early stage.
Fig 2. A sick cell and a plea for help, defenses engage
It turns out that coronavirus infection has 3 stages. Stage 1 is an infected person who has no symptoms. Stage 2 is an infected person with mild symptoms and stage 3 is an infected person with severe symptoms. At present 15 to 20% of total infected people progress to severe symptoms (stage 3). This number is higher in persons above age 65 years of age. Thus, stage 1 and some stage 2 infected patients could, in theory limit the infection.

Things, yet are not straightforward as it were. The coronavirus has tools to counteract the very mechanism that can help humans. In a strategic countermove, the covid-19 virus blocks the ability to make interferon. It neutralizes the 'sensor' proteins inside the cell. This handicaps the cell to detect the virus and interferes interferon production. Besides effect on interferon production, the viruses cripple the response to the rest. This allows the virus to keep infecting more cells, spreading fast causing damage. The virus copies itself into millions of viruses, setting a stage for a battle where both armies number in millions.

References:
- Li G, Fan Y, Lai Y, et al. Coronavirus infections and immune responses. J Med Virol. 2020;92(4):424‐432. doi:10.1002/jmv.25685
- Prompetchara E, Ketloy C, Palaga T. Immune responses in COVID-19 and potential vaccines: Lessons learned from SARS and MERS epidemic. Asian Pac J Allergy Immunol. 2020 Mar 1;38(1):1-9.
- Fung, To Sing, and Ding Xiang Liu. "Human Coronavirus: Host-Pathogen Interaction." Annual review of microbiology 73 (2019): 529-557.

Next section: Ch 2. No defenders to help - Immunity to coronaviruses in context of COVID-19
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