BEST Predictor of COVID Disease SEVERITY? 

By  Dr. Mike Hansen

BEST Predictor of COVID Disease SEVERITY?

Some people with COVID do just fine, Others die. And then there is everyone in between. So what determines disease severity?
Yeah, most of us know the risk factors by now. It’s mostly older age, being a male, obesity, diabetes, high blood pressure. But not everyone with severe COVID fits that mold; for example, there was the case of the 28-year-old female who needed to have a double lung transplant in Chicago.

But what about the number of viral particles you are exposed to?
Or how many viral particles invade your body before the immune system defeats it?

Predictor of COVID

The number of viral particles that land on your mucus membranes when a covid infected person coughs or sneezes is the viral dose. An infection can start with a few viral particles. However, the higher the dose, the more likely the immune system will not clear all viral particles, and infection will take hold. The viral dose required to make you sick seems very low for COVID as it is spread through casual contact. The CDC changed its definition of close contact to a cumulative exposure of 15 minutes or more in contact with an infected person because it appears that even a series of small exposures may also cause disease.

We may not know the minimum infectious dose of SARS-CoV-2 needed to result in illness or whether multiple small doses or a single large dose is more likely to lead to severe disease. The amount of virus someone gets into their system depends not only on the duration you are exposed to someone with the covid virus but also the viral concentration you are exposed to and proximity. And this is why social distancing and wearing masks is so necessary to mitigate this process.

Viral load is the level of replicating virus in the body and is measured by copies per ml. We can determine whether the SARS-CoV-2 virus is present in the human body by collecting samples from the nose, respiratory tract, blood, or urine.

When the SARS-CoV-2 virus reaches the respiratory tract and binds to the ACE2 receptors on human cells, viral particles enter respiratory cells and reproduce, specifically in Type II alveoli. The newly made viral particles infect other cells, and the cycle continues. This cycle can carry on and exponentially increase the number of viral particles until the immune system has a chance to tame it and hopefully stop the replication process. Whatever that number maybe, this is what we refer to as the viral load.

Studies have shown that the higher the viral load in nasopharyngeal swabs or the blood, the more severe the disease will be, with higher viral loads equating to two times or higher odds of needing a breathing tube (intubated). And this is regardless of age, other risk factors, and severity of illness at the time of presentation to the hospital. Quantifying the viral load is a tool physicians can use for risk stratification.

The PCR Test for COVID
A reverse transcription-polymerase chain reaction test (RT-PCR test) is used to detect the SARS-CoV-2 infection on a swab of nasal secretions. A lab technologist prepares the swabs for processing and adds the fluid from the swabs and other chemicals to the PCR machine. The PCR machine goes through a series of heating and cooling cycles, during which it makes copies of any viral RNA in the sample. Each time the PCR machine goes through its cycles, it doubles the number of RNA strands present.

The PCR machine can report whether the covid virus was present and, if so, how many cycles it had to go through to amplify the RNA enough to detect the cycle threshold. If no virus is present in the sample, the PCR machine can go through innumerable amplification cycles, and the virus will still not be current. If low virus levels are present, more PCR amplification cycles will take enough RNA to make the SARS-CoV-2 sample detectable. If large amounts of SARS-CoV-2 are in the sample, fewer amplification cycles will be required to get an observable sample. More irregular amplification cycles to get a detectable level of RNA equals a higher viral load.

Doctor Mike Hansen, MD
Internal Medicine | Pulmonary Disease | Critical Care Medicine

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