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In support of KarinCA’s assertion I decided to do the forbidden and unthinkable, never done before thing: voice a non-professional opinion on weighty medical matter: does hydroxychloroquine (HCQ from now on) have benefit in treatment of Covid-19? I will treat in-vitro studies as if they were verified, which they are not. BTW: All that follows has been said here before. Maybe not in a single entry.

Step and Reference 1:
“Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro” a.k.a. The Chinese letter to Cell Research / Nature

In-vitro study using Vero E6 (green monkey kidney) cells showed that HCQ inhibits corona virus proliferation by about 50 to 80 % depending on test used. This was markedly better result than obtained with current favorite, Remdesevir.
At this point is seems that HCQ has something going for it, and more so than Remdesevir. But…

Step and Reference 2:
“Chloroquine does not inhibit infection of human lung cells with SARS-CoV-2” a.k.a. German accelerated paper in Nature.

Looks like Germans have totally opposite opinion on HCQ to that of Chinese. Well, actually not. This needs some explaining. An edited quote from the German paper follows:

“Chloroquine and hydroxychloroquine elevate endosomal pH and inhibit viruses that depend on low pH for cell entry. SARS-CoV-2 can employ pH-dependent and pH-independent pathways for entry into cells. Thus, SARS-CoV-2 spike protein (SARS-2-S), which mediates viral entry, is activated by the endosomal pH-dependent cysteine protease cathepsin L (CatL) in certain cell lines. In contrast, entry into airway epithelial cells, which express low levels of CatL depends on the pH-independent, plasma membrane resident serine protease TMPRSS2. Importantly, TMPRSS2 activity is essential for viral spread and pathogenesis in the infected host.”

It turns out that SARS-Cov-2 entry into Vero E6 cells is facilitated by CatL pathway which is, as stated above, pH depended. When alternate pathway is present ie. TMPRSS2 is activated in Vero E6 cells (engineered Vero-TMPRSS2+ cell line) HCQ does not inhibit viral entry into cell. So, German’s did not disagree with the Chinese, they pointed out limitations, so to speak.

Lofty conclusion based on pre-clinical data, or who needs clinical studies anyway!
Here the story gets iffy, I start to rely on my own brain power, which is like my late dad’s beloved Ericsson outboard motor – sputtering. I went surfing and found some evidence that fits nicely to above findings – reference 3, tissue expression of TMPRSS2. This link has a pretty table showing our current knowledge of TMPRSS2 tissue expression. Notice that according the table TMPRSS2 is not expressed in blood. Okay, it is somewhat dangerous to say that. The table is, as I said, OUR CURRENT UNDERSTANDING. Who knows, maybe tomorrow, somebody publishes a paper firmly showing that TMPRSS2 is expressed all over blood cells. But, for now, I proceed as my current knowledge dictates. No TMPRSS2 in blood.

And here we are. It is plausible that hydroxychloroquine prevents viral entry into blood by altering endosomal pH level in blood cells. That would render Covid-19 to be something akin to bad pneumonia. Treatment wise there are some caveats.
1. To be effective HCQ needs to be administered really, really early in the disease progression. If SARS-Cov-2 gets a good foothold in blood the game is probably over.
2. Because viral infection in lungs is not affected by HCQ patients are still infectious. Plus, serious scarring of lung tissue is still possible.

All this is, of course, my opinion and as such… But, details in pro-HCQ clinical findings so far (and they are very anecdotal and scientifically flimsy, whatever the Good Doctor at Yale says) seem to support it. We should know better before the end of this year. There are number of well-designed (about time!) studies on-going.

Meanwhile, I do as all lonely, self-appointed geniuses do – become ornery and retire in my bedroom to wait my inevitable, posthumous Nobel award (which will never come, Nobels are bestowed only on living)

Here are the links.
1. https://www.nature.com/articles/s41422-020-0282-0
2. https://www.nature.com/articles/s41586-020-2575-3
3. https://www.proteinatlas.org/ENSG00000184012-TMPRSS2/tissue
And the paper by the Good Doctor at Yale (who did not read my reference 2 before writing his opinion. It is that new)
https://academic.oup.com/aje/article/doi/10.1093/aje/kwaa093/5847586