Thread by @LauringLab

Been thinking more about this piece from @kakape this morning and have some thoughts to share. So thought I'd do a Xmas eve thread about SARS-CoV-2/COVID19 and immunocompromised hosts. (1/x)
sciencemag.org/news/2020/12/u…

I emphasize that I respect the stated opinions out there and don't have doubts about data or what they may show. Just feel there's a perspective missing from the conversation. What can I bring to conversation? I am an infectious disease physician and study virus evolution. (2/x)

I have taken care of patients with COVID19 who have a range of immunocompromising conditions. I have also published on within host evolutionary dynamics of viruses. We published a preprint in Sept and subsequent JID paper on long term evolution in lymphoma patient. (3/x)

If this is TLDR btw, stop here. The point is we should be cautious and not get ahead of ourselves. First - and I concede that this is a pet peeve - the term "immunocompromised" is easily thrown about, but it's really complicated. Diff conditions and treatments can affect... (4/x)

Your immune system in very different ways. Are cancer chemo patients IC (immunocompromised)? Yes depending on their chemo. Are they different from heme malignancy patients on chemo? Very much so. Are solid organ transplant patients different? Yes. How about lupus on HCQ? (5/x)

I've seen organ transplant patients handle COVID19 no sweat. I've seen lymphoma patients shed for months. I've seen people on biologics do fine. I've seen patients with leukemia has slightly prolonged course, but nothing concerning. (6x)

OK, so what? Well, we need to be careful in our discussions. And be honest with ourselves about the evidence base and clear in our communication. Particularly so, because in the COVID19 media environment, things get quickly out of hand. (7/x)

The B.1.1.7 lineage has lots of mutations and is unusual. It is plausible that this could result from prolonged within host replication. And, yes, patients with lymphoma and poor B cell function can have prolonged replication. (8/x)

And yes, convalescent plasma can apply a selective pressure. However, I think it is really prolonged replication rather than antibody selection that is at play in these mutation accumulations. But that's a long discussion about the strength of selection vs. time. (9/x)

OK back to the point. And we know that some of the mutations in IC hosts can affect serum neutralization (but people need to be clearer on magnitude of effect, e.g. 4x or 10x, and whether it constitutes "escape"). But, There are lots of people who've had conv plasma...(10/x)

Monoclonals etc. even IC hosts, who do not have evidence of viral escape. Our report, patient didn't even has any nonsynon mutations in spike. So, yes you can draw a line from IC host have long term evolution to plasma can (11/x)

select for mutations to these mutations can *sometimes* mediate a change in the *degree* of neutralization to lineage of concern. But we need to be clear about all the paths out there that don't connect the dots. (12/x)

And be honest that we are connecting dots with very incomplete information and we could be connecting the wrong dots. That's not a criticism of the process, that's science after all. But caution needed. (13/x)

So why am I spending time writing about this. I get concerned when I see quotes like this. Again, I am not getting on Jeremy Farrar's case or saying he is wrong (really I'm not) (14/x)

But, I immediately started thinking of who this would apply to? All cancer chemo patients? All patients on B cell directed biologics? All patients with any condition affecting their immune system? Diabetes? And how long do you isolate? Until RNA negative? Culture negative? (15/x)

And is that reasonable? Does that fit with the current level of evidence? What are the downsides for our patients here (being locked in a room away from family for 100 days). Is that appropriate given the evidence available? (16/x)

And, I worry about the message physicians may take. Should we not treat people - or certain people - with convalescent plasma or monoclonals, because of this issue? (again, for which evidence is far from complete). (17/x)

IC hosts are priority for the monoclonal Ab at my institution. Should we stop? I don't think so. Am I being alarmist about implications? Nope, physicians already asking me about this. (18/x)

Again, I think this is an important issue, that scientists are doing great work, that the issues at play need discussion. No easy decisions. But we owe it to decision makers to be clear and not get too far ahead of data. (19/x)

Any thoughts @PergamIC @mugecevik ?