I had no scheduled time today for journal reading, but, when I saw this article I had to take a break from other stuff and give it a read. Apologies if I missed anything. As always, point out if I did, or if I misinterpreted anything.

https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(24)00171-3/fulltext

I find this interesting, because next to a large-scale autopsy study(I do not know why this hasn't been done), this is probably the next best thing to look for viral persistence.

In their own words:

"This single-centre, cross-sectional cohort study was done at China–Japan Friendship Hospital in Beijing, China, following the omicron wave of COVID-19 in December, 2022. Individuals with mild COVID-19 confirmed by PCR or a lateral flow test scheduled to undergo gastroscopy, surgery, or chemotherapy, or scheduled for treatment in hospital for other reasons, at 1 month, 2 months, or 4 months after infection were enrolled in this study. Residual surgical samples, gastroscopy samples, and blood samples were collected approximately 1 month (18–33 days), 2 months (55–84 days), or 4 months (115–134 days) after infection. SARS-CoV-2 was detected by digital droplet PCR and further confirmed through RNA in-situ hybridisation, immunofluorescence, and immunohistochemistry. Telephone follow-up was done at 4 months post-infection to assess the association between the persistence of SARS-CoV-2 RNA and long COVID symptoms."

So, in short, what did they find? In patients who no longer tested positive via nasopharyngeal RT-PCR, a lot of viral persistence, in both "viral RNA" and "subgenomic RNA" but not universal viral persistence. Of course, they were unable to search all tissues in anyone's body, so that's not to eliminate the possibility that it was elsewhere in any test subject.

The big question to me here, and at least on my first read I think they were careful not to discuss it; was the viral RNA replicating? Given the lack of discussion on it in the article, let's just move on, but it's in the back of my mind.

Viral RNA was found, overall, in 30% of solid tissue samples collected at one month, 27% of those at two months, and 11% of those at 4 months. Further, additional subgenomic RNA was detected in 61% of samples that had viral RNA.

Also, viral RNA was detected in blood plasma, white blood cells, and peripheral blood mononuclear cells(think T cells and B cells here) of 9 patients, all of whom were immunocompromised, but none in 10 patients who were immunocompetent. Of course, everyone is immunocompetent until they're not.

Importantly, "Detection of viral RNA in recovered patients was significantly associated with the development of long COVID symptoms" and "Patients with higher virus copy numbers had a higher likelihood of developing long COVID symptoms."

There's an awful lot here, but a few other things were interesting to me:

- An even split, essentially, in long COVID between men and women.

- 78% of the patients with long COVID had 3 vaccine doses(I'm sorry, vaccination does not mean you can't get long COVID and it can't be said enough) while 86% without long COVID had 3 vaccine doses. Only 6% were unvaccinated in both the long COVID and no long COVID cohorts.

- 46% of the long COVID cohort were given one of oseltamivir, baloxavir, nirmatrelvir–ritonavir, famciclovir, and ganciclovir, while 52% of the no long COVID group were.

- Viral RNA was found in:

liver, kidney, stomach, intestine, brain, blood vessel, lung, breast, skin, and thyroid

but not pancreas, gallbladder and appendix.

- "Furthermore, to explore whether any difference in viral load was due to different concentrations of the SARS-CoV-2 receptors ACE2 and TMPRSS2, we compared the expression levels of ACE2 and TMPRSS2 in tumour tissues and paratumour tissues, and the results showed that the mRNA levels of ACE2 (p=0·83) and TMPRSS2 (p=0·49) were not significantly different"

- "Long COVID symptoms at 4 months were significantly associated with viral persistence at 1 month and 2 months post-infection but not at 4 months."

- "The host cell dysfunction caused by viral persistence might be a crucial aspect of long COVID pathogenesis."