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I'm seeing this making the rounds this morning. I have issues with it, specifically two of the claims.
1. It's never been shown whether re-positive patients are contagious or not. (It has)
2. That 1/32 patients had replicating virus. (Not really) https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/10.1001/jamainternmed.2020.7570
1. It's never been shown whether re-positive patients are contagious or not. (It has)
2. That 1/32 patients had replicating virus. (Not really) https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/10.1001/jamainternmed.2020.7570
Claim 1. Are re-positive patients capable of causing new infections? Nobody's looked at this.
Actually, they have. Back in May, the South Korean CDC studied nearly 300 re-positive patients. None shed infectious virus & none were linked to new cases. http://www.kdca.go.kr/board/board.es?mid=a30402000000&bid=0030
Actually, they have. Back in May, the South Korean CDC studied nearly 300 re-positive patients. None shed infectious virus & none were linked to new cases. http://www.kdca.go.kr/board/board.es?mid=a30402000000&bid=0030
Claim 2. 1/32 patients had replicating virus. https://twitter.com/Ryan_Mac_Phd/status/1327242192474288128
Technically they had replicating viral RNA, since they detected subgenomic RNA in that patient. Subgenomic RNA is only produced when the virus is replicating.
However, subgenomic RNA alone is not the same thing as infectious virus.
However, subgenomic RNA alone is not the same thing as infectious virus.
Viruses encode 2 types of matter-of-factly-named proteins: structural and non-structural. Structural proteins make up the physical structure of the virion (virus particle). Non-structural proteins do various intracellular jobs like copy the genome, evade innate immunity, etc.
During virus replication, subgenomic RNA (sgRNA) is transcribed when the genome is being replicated. sgRNAs encode the structural proteins (spike, nucleocapsid, membrane, and envelope), which are made in large quantities since they are used to package new genomes into virions.
But there are a bunch of steps after sgRNAs are made (transcribed). These are translated into the structural proteins in the endoplasmic reticulum and trafficked through the Golgi apparatus, where they are assembled into mature virions before budding out of the cell.
So if sgRNA is transcribed but all that translation, trafficking, assembly, and egress from the host cell doesn't happen, then sorry, no virions capable of infecting other cells for you. sgRNA is a measure of viral replication, but it is not a measure of infectious virus.
And viruses are not the finely tuned molecular terminators that they are often made out to be. They are imperfect & abortive replication occurs all the time. So while sgRNA can be used as a proxy for replication (as in vaccine challenge studies) it's doesn't measure infectivity.
And sometimes sgRNA is associated with infectious virus, but sometimes not. This study looked at both sgRNA and cultured virus. Sometimes there was infectious virus cultured when sgRNA was present, and sometimes only sgRNA was detected.
https://wwwnc.cdc.gov/eid/article/26/11/20-3219-t2
https://wwwnc.cdc.gov/eid/article/26/11/20-3219-t2
In the JAMA study, the re-positive patient with detectable sgRNA was seropositive, meaning they mounted an antibody response to infection. In people with high levels of neutralizing antibodies, those will effectively bind and render progeny virions as they bud from the host cell.
Furthermore, if the patient had antibody responses, they probably also had T cell responses. I'd bet that CD8+ "killer" T cells, which kill infected cells, just hadn't gotten to the cells with residual sgRNA being transcribed.
To the authors' credit, they acknowledge that they can't conclude that the re-positive patient was contagious based on the presence of sgRNA alone. But this is a cautionary tale about relying on molecular assays (PCR) to make conclusions about infectivity.
It all comes back to the oldest trick in the virologist's book: if you want to find infectious virus, you gotta do the plaque assay.