Covid-19+, when are you not infectious?

"The likelihood of recovering replication-competent virus also declines after onset of symptoms. For patients with mild to moderate COVID-19, replication-competent virus has not been recovered after 10 days following symptom onset (CDC, unpublished data, 2020; Wölfel et al., 2020; Arons et al., 2020; Bullard et al., 2020; Lu et al., 2020; personal communication with Young et al., 2020; Korea CDC, 2020). Recovery of replication-competent virus between 10 and 20 days after symptom onset has been documented in some persons with severe COVID-19 that, in some cases, was complicated by immunocompromised state (van Kampen et al., 2020)."

Many have asked me about this issue. The CDC is foolish to make this statement. They should know better...a lot better.

People want to know that when is person no longer contagious. And we can make estimates based on clinical data on transmission.

These studies cited above are about pts who have repeat Covid tests and are still positive.

So, when is the virus no longer replication competent?

If the test is the RT-PCR assay, then never, really, is the true answer.

Real-time PCR measure only DNA.

The genomic viral RNA is converted to DNA and the Q-PCR or real-time PCR amplifies the cDNA (copied DNA).

As you can imagine, human bodies and all other animals and plants don't like RNA wandering around. 

Further, RNA, which differs only in a single hydroxyl group in each base, is easily attacked both chemically and enzymatically.

DNA, on the other hand, is not. 

This means DNA is much hardier than RNA and explains why Nature chose DNA to store genetic information. However, our cells use RNA in every other step of making proteins. So, we humans don't like random RNAs floating around.

When working with RNA, researchers go to great lengths to make sure they don't introduce any RNAses or chemicals which will degrade their RNA specimen.

When working with DNA, you just want to accurately pipette. 

They were no dinosaur RNAs in the Jurassic Park's mosquitoes.

So, why is this all relevant?

Well, because any viral RNA detected in or on a human being has to be protected in a virion (virus). 

There really is no such thing as free RNA, because it is quickly degraded by our RNAses, enzymes designed solely to attack free RNA. The human body doesn't want RNAs just floating around, so it goes to great lengths to attach RNAs, which are just hanging around.

So, SARS-CoV-2 RNA is only detected when it is protected in a virion. (Virion is just another word for virus)

The first steps after swabbing a person's throat are to elute the virion from the swab and extract the RNA. 

All viruses protect their genomic RNA or genomic DNA will an envelope and often a viral membrane. Inside the virion, the RNA is protected against the harsh environment, that is the human body.

Obviously, this means that any RNA detected in a person's throat or nose is inside a virus and presumably replication competent.

HOWEVER, since infectious diseases is math based, there is probably some level of SARS-CoV-2 virus in the throat when a person is no longer contagious, we just don't know how to measure that level. 

The papers that use virus culture to determine a person's infectivity are simply stupid.

Virus culture and infectivity a person have nothing to do with each other. 

For instance, it is very hard to grow HIV from a person's blood plasma, no matter the viral load.

It is VERY easy for a person to become infected with that same plasma. 

Virus cultures are notoriously insensitive, especially when compared with nucleic acid amplification assays, such as RT-PCR and PCR. 

This is true for every example I am aware of.

It is very hard to culture VZV from shingles lesions (even when the virus involves your face), yet the PCR is always positive. 

No one in their right mind would try to culture HSV-1 or HSV-2 from cerebrospinal fluid, yet we use PCR to rule out these infections, meaning PCR for HSV-1 and -2 is very sensitive and virus culture is extremely insensitive. 

So, when a person is positive for SARS-CoV-2 RNA, that person is still making virus and that virus is replication competent, as far as we know.

We use the term, "viral shedding". It's an idiotic term, which implies the person is making virus still, but isn't sick.

We use "viral shedding" for many viral infections. 

In every instance I am aware of, virus shed from the human body is replication competent.

So, when a person "sheds virus", it isn't so benign for the people they infect.

Most genital herpes infections occur from "viral shedding" in one sex partner, who gives the virus to another. 

CMV virus shedding also can result in infection. 

Many gastrointestinal viruses are shed for weeks to months, leading to many more infections of people who come in contact with the stools of virus shedders.

In Medicine, we rarely use the phrase "WE KNOW". We always hedge our predictions. But back to the HIV-1 example, we KNOW that if a person has a plasma viral load < 200 copies/ml for a few months, then that person cannot infected someone through sexual acts. We don't know and haven't tried to give blood from a person with detectable virus but less than 200 copies/ml of plasma can transmit HIV-1 through a blood transfusion. Obviously, we feel they can. But the vast clinical data from several countries give us ability to say we KNOW that these people cannot transmit HIV sexually.

In short, just because a virus culture is negative does not mean that virus detected via RT-PCR is not alive. Trust me, it most probably is. Why would it be defective? Why would your body make infectious SARS-CoV-2 and then suddenly start making dead virus? It wouldn't unless you gave a powerful antiviral, like a protease inhibitor in HIV-1, which allowed for the production of virion, but made them non-infectious.

So, how do we know when a person is no longer infectious?

Well, for SARS-CoV-2, we don't yet "KNOW", but we do have plenty of data on lack of transmission, especially in mild cases, after 10 or 14 days.

Once again, clinical data are the most important data to consider. Basically, the CDC is using lab data to fit the clinical data. That's a waste of time. The clinical data speak for themselves and don't need laboratory confirmation.

Stephen M. Smith, M.D. and former virologist