Vaccines that Work Provide Hope for an End to the Pandemic

bioserendipity
5 min readNov 29, 2020

Vaccines based on the Spike protein provide protection against COVID-19. Image shows viral particle with the S protein in red in the center. On each side is the 3-D structure of this protein complex showing each S protein in the complex in a different color. [Compilation by Nancy R. Gough, BioSerendipity, LLC

Clinical trial results from 3 vaccines show that the vaccines have good efficacy. This means that they protect the people who receive the vaccine from getting severe COVID-19. Two of the vaccines are based a new technology that has not been used before in approved vaccines. The technology is new, however, it is not completely different from some other vaccine technologies. The two vaccines deliver instructions (in the form of nucleic acid) for your own cells to make a protein that the virus makes, so your body will recognize when the virus is present and prevent it from infecting your cells

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An imbalanced immune response appears to be the key to whether a person develops severe COVID-19 with pneumonia and other complications such as coagulopathy (excessive formation of blood clots), impaired kidney function, neurological issues, and heart complications. Multiple mechanisms likely contribute to the variability in the immune response within the population and determine whether a person has asymptomatic disease, mild disease, or severe disease with potentially fatal complications.

Obesity is associated with a pro-inflammatory state. Aging is also associated with changes in the immune system. Could there be a common change in inflammatory mediators in both of these populations that contributes to the increased risk of developing severe COVID-19?

Dr. Ajay Gupta, MD, MBBS (Chief Scientific Officer of Rockwell Medical, Inc) thinks so. He thinks the connection is prostacyclins, in particular prostaglandin D2 and thromboxane A2. Prostaglandin D2, in particular, increases with age and obesity, providing a potential molecular link between these two conditions and the risk of developing severe COVID-19.

Prostaglandin D2 has complex effects that vary depending on which cell is responding and the receptor that it activates. The effects of prostaglandin D2 mediated by activation of one of its receptors (DP2) can contribute to symptoms of severe COVID-19. Signaling through DP2, prostaglandin D2 can cause an impaired antiviral immune response called the interferon response and can suppress the activity of multiple immune cells. Together, these effects prevent the body from clearing the virus and virally infected cells. Thus, these immune-suppressing effects of DP2 signaling let the virus replicate and cause severe pneumonia in the lungs and potentially infect and damage other tissues. Additionally, prostaglandin D2 signaling through DP2 triggers bronchoconstriction that makes it harder to breathe

As the cold weather comes, I am beginning to plan how to socialize safely. It will be harder to do outside visits or visits with the doors and windows open to keep ventilation high. This means I need to think more carefully about who is inside my social interaction bubble. Each household that is part of the circle extends my circle.

It rapidly becomes a complex diagram of overlapping circles. It only takes one person in any of these overlapping circles to contract SARS-CoV-2, with or without symptoms of COVID-19, and the virus can get into my circle.

So, as we move into the cooler weather, knowledge is key. Know where the people you socialize with have been. Know how many other people they have encountered, especially in close proximity. More people means more distance between you and them and keep those masks on

As researchers evaluate patients that develop severe COVID-19, the disease caused by the coronavirus SARS-CoV2, they are discovering answers to why some people become so critically ill and others do not. A pair of papers in Science by international teams of scientists led by Jean-Laurent Casanova reports reasons for why ~14% of severe cases of COVID-19 occur. Importantly, this information is clinically useful and will help screen at-risk individuals, prioritize vaccination, and treat patients. Additionally, these findings support a key theory regarding why COVID-19 shows so much variability: Interferon signaling varies within the population.

Genetic Variation that Compromises Interferon Signaling

In the first study, researchers proposed that genetic variations in the population may underlie susceptibility to severe COVID-19 and established the COVID Human Genetic Effort to identify such genetic mutations

Lots of confusion out there today. Yesterday, I saw a tweet in the news part of Twitter titled, “CDC says recovered COVID-19 patients will have immunity for about three months.”

Tweet on the news part of Twitter that misrepresents CDC guidelines for testing people who recover from COVID-19.

Newsweek had a similar headline: “Those infected with COVID-19 are immune for just 3 months, CDC says”

Both headlines are misinterpretations of what CDC meant. The CDC did not state that immunity only lasts for 3 months or always lasts for as long as 3 months.

We have no idea how long immunity will last in people who become infected with SARS-CoV-2 and get COVID-19. We do not know if immunity persists for different lengths of time in people who have asymptomatic disease or people who develop and recover from severe disease.

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